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Chapter-Basics of Pharmacy

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 Chapter – One

ABC of Pharmacy

Pharmacy: The word pharmacy is derived from the Greek word “Pharmakon”, meaning
medicine or drug. According to the dictionary pharmacy is defined as “the art and science of
preparing and dispending drug” pharmacy is a health profession concerned specifically with the
knowledge of drugs and wisdom in their uses. This profession links the health with chemical
sciences. Modern pharmacy services include patient care, clinical services, ensuring safety and
efficacy of medications, and providing patients counseling and drug information. Today, the
pharmacists are also considered as health practitioners who are responsive to the needs of
patients.
Pharmacist: Pharmacist is an expert on drugs and medicines. Pharmacist is qualified person
who for fees, salary or other consideration paid to him, manufactures, prepares, distributes, sells
or serves any prescription for any medicine, drug or pharmaceutical preparation. He is a skilled
and highly-trained healthcare professional.
A qualified person who has got registration from Pharmacy Council of Bangladesh (PCB) or
from any pharmacy related regulatory bodies of other countries is called Registered Pharmacist
(RPh).
Types of pharmacy practice areas:
Pharmacists play professional roles in different aspects of drugs and diseases management.
Pharmacy practice, a discipline of pharmacy, helps in the development of professionalism in
pharmacists. As drug experts, pharmacists are mainly engaged in diseases state management,
extemporaneous compounding, health psychology and patient counseling, patient care, drug
abuse prevention, prevention of drug-drug and drug-food interactions, minimizing adverse drug
reactions, solving problems of incompatibilities such as pharmaceutical, therapeutic and
pharmacological incompatibilities, etc. Clinical interventions are also under the jurisdiction of
pharmacists, where they have the right to refuse drug dispending under certain circumstances, to
recommend changes and or additions of drugs to patient’s pharmacotherapy, to adjust the dosage
as per requirement, to manage the total parenteral nutritions (TPN) of the patient, etc. However,
there are a number of pharmacy practice areas where pharmacists can render professional
services. The major areas are:
a) Hospital pharmacy
b) General pharmacy
c) Industrial pharmacy/ Compounding pharmacy
d) Whole sale pharmacy

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 e) Retail pharmacy
f) Clinical pharmacy
g) Veterinary Pharmacy
h) Nuclear pharmacy
i) Nutritional pharmacy/Functional foods pharmacy
j) Herbal/Traditional/Complementary pharmacy
k) Military pharmacy
l) Forensic pharmacy
m) Consultant pharmacy
n) Tele/ Internet pharmacy
o) Pharmacy informatics
p) Teaching and research
Scopes of pharmacy:
According to the National Association of Boards of Pharmacy Model Practice Act of 1977 of
USA, “The Practice of Pharmacy” shall mean the-
 Interpretation and evaluation of prescription orders;
 Compounding, dispending, labelling, of drugs and devices;
 Prescription in drug selection and drugs utilization reviews;
 Proper and safe storage of drugs and devices and the maintenance of proper records;
 Responsibility for advising of therapeutic values, dosage schedule, uses, side effects and
toxicity of drugs;
 Performing of those acts, services, operations or transactions necessary in the conduct,
operation, management and control of pharmacy.
Moreover, the areas and scopes where a pharmacists can build up his/her career can be
summarized as follows:
1. As community pharmacist.
2. As institutional pharmacist in government and private hospitals, health maintenance
institutes, clinics, nursing homes, etc.
3. As retail/ wholesale pharmacist.
4. As industrial pharmacist in research and development, production, quality control, quality
assurance, marketing, promotions and sales, etc.
5. As government employee in army, navy or air force as commissioned or
noncommissioned officer, public health service, civil service, drug administration, central
drugs store (CSD), narcotic department, department of agriculture and other divisions,
etc.
6. As teacher, instructor and researcher in pharmacy educational institutes.
7. As journalist in pharmaceuticals and drugs information.
8. As manager or director of different national and international organization such as World
Health Organization (WHO), United Nations International Children’s Emergency Fund
(UNICEF), etc.

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 9. As instructor/ programmer of school and social health program.

Future of pharmacy:
The old concept of pharmacy as the place of simply dispending and selling of medicines has
already been changed. Now, pharmacists are efficiently working in hospitals, clinics, industries,
research institutes and other governmental and non- governmental organizations. In future, well-
trained pharmacists are expected to be more important personnel by providing their specialized
knowledge and skill to improve the total health care system. In Australia, pharmacists are
involved in comprehensive Home Medicine Reviews and receive remuneration from the
Australian Government. In the UK, pharmacists who undertake additional training are obtaining
prescription writing rights. In USA, the Doctor of Pharmacy (Pharm D.) degree is a prerequisite
before entering to pharmacy practice.
Future of pharmacy profession in Bangladesh:
 The practice of pharmacy will become ever more important in the developed and developing
country with more potent drugs coming to the market.
 Pharmaceutical care will be an important component of health care as the awareness of
adverse drug reaction. Pharmacogenomics and pharmacoeconomics and socioeconomic
factors associated with health and diseases are being recognized.
 Rising longevity will increase dependence on medicines and hereby on the pharmacists.
 Regulatory affairs and Drug administration will play more important role in the country.
 Waiver of WTO regulations and restrictions has given an important opportunity to export
drugs to develop and developing countries.
 Countries own drug consumption will see a phenomenal increase with the rise in purchasing
power of the people.
 So the pharmaceutical industries will witness a rapid increase in growth resulting in more
demand of manpower in the industries.
 Global concern for better health care at an affordable price involving all types health
personnel, doctors, pharmacists, nurses, social scientists, economists will favor the
developing countries having knowledge and skill.
Pharmacy degree and curriculum:
Bachelor of Pharmacy (B. Pharm.): It is an undergraduate academic degree in pharmacy. This
degree is awarded following a four-year undergraduate pharmacy program and is the basic
degree required for registration to practice as pharmacist in many countries. In Bangladesh, those
who have completed 10-year school and a 2-year college education in science group are eligible
to get admission to the B. Pharm program. The curriculum of B. Pharm program includes:
 Inorganic Chemistry
 Organic Chemistry
 Physical pharmacy
 Pharmacognosy

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 Microbiology
 Physiology Anatomy
 Pathology
 Biochemistry and Molecular Biology
 Pharmaceutical Biotechnology
 Medicinal Chemistry
 Pharmaceutical Analysis
 Pharmaceutics
 Pharmaceutical Engineering
 Biopharmaceutics and Pharmacokinetics
 Hospital pharmacy
 Clinical pharmacy
 Community pharmacy
 Toxicology
 Pharmaceutical Marketing and Management
 Pharmaceutical Marketing and Sales
 Pharmacy law and Ethics, etc.

Master of Pharmacy (M. Pharm.): It is considered as a postgraduate degree after the B. Pharm.
degree in Pharmacy. In many countries it has superseded a B. Pharm. degree as the prerequisite
for registration for practice as Pharmacist. However, in UK the M. Pharm. degree is offered
mainly in the following areas:
 M. Pharm. (general program)
 M. Pharm. in Pharmaceutical Chemistry,
 M. Pharm. in Pharmaceutical Technology
 M. Pharm. in Clinical Pharmacy and Pharmacology
Moreover, Master of Philosophy (M. Phil.) degree (a 2-year postgraduation program) and Doctor
of Philosophy (Ph.D.) are also offered as specialized degree by research.
Doctor of Pharmacy (Pharm.D.): In USA, this is the first professional degree for practicing
pharmacy. Previously B. Pharm. was the first the first professional degree for pharmacy practice
in USA, but in 1990, the American Association of Colleges of Pharmacy (AACP) decided that a
pharm.D. degree would be the first professional degree to get license as Registered Pharmacist
(RPh) for pharmacy practice.
According to the Foreign Pharmacy Graduate Equivalency Examination (FPGEE) Committee:
“Beginning January 1, 2003, the National Association of Boards of Pharmacy (NABP) ask
foreign educated pharmacists to have earned their professional degree from a five-year program
in order to apply for ‘Foreign Pharmacy Graduate Examination Committee (FPGEC)
Certification’. The decision is said to have been prompted by introduction of the 6-year doctor of
pharmacy (Pharm.D.) curriculum in the United States. In USA, the NABP has created a standard
examination system known as NAPLEX (North American Pharmacist Licensure Examination) to

4
assess an individual’s competency and knowledge so that he or she may be given a license to
practice pharmacy.
Pharm.D. program is composed of a five-year integrated course in Pharmacy followed by one-
year/two-year internship as residency in hospitals. Pharmacy Council of India has permitted few
universities to start Pharm.D. course from October 2006. The program consists of 5-year course
and one-year internship in hospital. In 2003 Pakistan Pharmacy Council has also accepted
Pharm.D. as the mandatory new first-professional degree.
Diploma in Pharmacy: This is a three-year pharmacy program. Pharmacy Council of
Bangladesh (PCB) has permitted many institutes to run the diploma program. Those who have
passed the secondary school certificate (SSC) examination in science group are eligible to get
admission in this program. The curriculum of Diploma in pharmacy includes: Bengali, English,
Chemistry, Physics, Mathematics, Microbiology, Pharmacognosy, Pharmaceutical Chemistry,
Pharmaceutics, Pharmacology, Community Medicines, Integrated Health care, General hospital,
and Community Pharmacy (GHCP) etc. The PCB directly conducts the examination of this
program and provides ‘B’ category registration to those who successfully pass diploma in
pharmacy course. In UK and USA, many universities and institutes also offer diploma or higher/
postgraduate diploma in pharmacy, hospital pharmacy, clinical pharmacy, industrial pharmacy,
analytical pharmacy, etc. A number of courses are also available for Pharmacy Technician in
these countries.

History of Medicine and Pharmacy

History of Pharmacy: Diseases and illness have been accompanied with the creation of
mankind. However, the diseases and the treatment provided to the mankind at the prehistoric era
had not been documented. During that time, people used to believe on the supernatural power
and that the sickness/disease was due to the God’s anger or due to evil forces. It is difficult to get
exact picture of the nature of medicine and pharmacy practice in prehistoric age as there is
limited access to recorded history on the substances that were used by the primitive man for
treatment purposes.
In the ancient time, diagnosis and treatment of diseases were provided by the same person. The
roles of physician, pharmacist and priest were often confined in one person. That’s why the
history of medicines has become inseparable from that of pharmacy. Actually, the history of
pharmacy is a large and complex story as it had taken different routes and approaches in different
civilizations and countries. Although, in the modern concept, the professional boundaries of
medical practitioner and the profession of pharmacy are well defined and separated by each
professional bodies, Pharmacy has firmly been grounded in science since the beginning of the
19th century. From that time, the inclusion of the subjects such as Pharmacognosy (the study of
the drugs of natural origin), Pharmaceutical/Medicinal Chemistry (synthesis and analysis of
drugs), Pharmaceutics (preparation of pharmaceutical dosage forms) and Pharmacology
(concerned with the actions, uses of drugs and medicines, etc.) was started in the pharmacy
education and training curriculum.

5
Due to the discoveries and development of new drugs and medicines, and the ways to prepare,
present and dispensing them, the emergence of the pharmacy profession came forward and
pharmacy as a separate profession has been evolved since the beginning of the 19th century.
However, to get exact historical features about the evolution and development of medicines and
pharmacy, it is necessary to focus on following historical eras:
A. Prehistoric ages
B. Ancient ages/Historical era
C. Middle ages
D. Modern time

Medicines, Drugs and Pharmaceuticals

Medicine: A medicine is a chemical preparation, which contains one or more drugs and usually
other substances (excipients, stabilizers, solvents etc.) besides the active drug to make them more
convenient to use, e.g. Paracetamol 500 mg Tablet, Diclofenac 50 mg tablet, Amoxicillin 500 mg
Capsule, etc.
Counterfeit medicine: Counterfeit medicine is one which is deliberately and fraudulently
mislabeled with respect to identity / or source. Counterfeiting of medicines can apply to both
brand and generic products. Generally, Counterfeit products may include products with the
correct ingredients or with the wrong ingredients having fake packaging.
Essential medicines: Essential medicines, as defined by the World Health Organization (WHO)
are "those drugs that satisfy the health care needs of the majority of the population; they should
therefore be available at all times in adequate amounts and in appropriate dosage forms, at a
price the community can afford."
Drug: A drug is a substance that acts on the living body to alter the physiological process and
are used for prevention, diagnosis, control and treatment of disease, e.g. Aspirin, morphine,
amoxicillin, chlorpheniramine, tetracycline, etc.
Crude drug: A crude drug is a natural drug of plant, animal, or mineral origin. That is collected,
drying, grinding, etc. but not chemical change. E.g. Alium cepa ethanol extract, etc.
Official drugs: Any drug which is included in the current issue of a pharmacopoeias or in the
formularies are called official drugs, e.g. Paracetamol BP, Tetracycline USP, Amoxicillin USP,
Ranitidine USP, etc.
Non-official drugs: A drug that have never been appeared in the pharmacopoeias or in the
formularies are called non-official drugs. This may be a new natural or synthetic drug, e.g.
Acrivastine, Bupropion, Zolpidem, etc.

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Un-official drugs: A drug that have been recognized in the pharmacopoeias or in the formularies
but not included in the current issue are called un-official drugs, e.g. Terfenadine, Thalidomide,
etc.
Control drug: Some prescription medicines are controlled under the Misuse of Drugs legislation
(and subsequent amendments). These medicines are called controlled medicines or controlled
drugs. Examples include: Morphine, Methadone, Benzodiazepine, Pethidine, etc.
Over-the Counter Drug (OTC): OTC drugs are drugs that have been found to be safe and
appropriate for use without the supervision of a health care professional such as a physician, and
they can be purchased by consumers without a prescription. These drugs are sometimes approved
under applications like new prescription drugs, but more often they are legally marketed without
an application by following a regulation called an OTC drug, e.g. aspirin (one of the oldest OTC
drugs), paracetamol, antacid, etc. Some toothpastes, some mouthwashes, some types of eye
drops, wart removers, first aid creams and ointments that contain antibiotics, and even
antidandruff shampoos are also considered as OTC drugs.
OTC drugs generally have the following characteristics:
 Safe and well-tolerated, and effective.
 Benefits outweigh their risks.
 Have little or no misuse or abuse potential.
 Consumer can use them for self-diagnosed conditions.
 Adequately labeled.
 Have to be primarily used to treat a condition that does not require the direct supervision of a
doctor.
Me-too drugs (MTD): A drug that is structurally very similar to already known drugs, with
only minor pharmacological differences is called me-too drugs. Sometimes MTDs are also called
‘follow-on’ drugs, e.g. Omeprazole and Esomeprazole, etc.
Legend drugs/prescription drugs: Medication, which may be dispensed only upon legal
prescription are referred to as prescription drugs or legend drugs, e.g. Cephradine, Gentamycin,
Tetracycline, Atenolol, Losartan, Clonazepam, etc.
Narcotic drugs: Drugs, which act on CNS to relieve pain but produce narcosis and addiction,
are called narcotic drugs, e.g. Morphine, Heroin, etc.
Misbranded drugs: The drugs, which are produced without permission of component/respective
authority and do not bear any approved brand names, are called misbranded drugs. Misbranded
drugs do not contain proper labeling and DAR (Drug Administration Registration) number.
Dangerous drugs: The drugs which form a habit, dependence and addiction after prolonged use
are called dangerous drugs, e.g. Barbiturates, Morphine, etc.
Thermolabile drugs: Drugs, which are destroyed, or degraded by heat or light are called
thermolabile drugs, e.g. Insulin, Streptokinase, Trastuzumab, Vaccines, etc.

7
Biological drugs: Drugs, which are obtained from biological sources, are termed as biological
drugs. Biological drugs are normally protein or peptide in nature and are not suitable for oral use.
They are antigenic substances and may cause hypersensitivity, e.g. Sera, Solution of serum
proteins intended for injection, Vaccines, Toxins, Antigens, Antitoxins, Insulin, Pituitary extract,
Adrenaline and Solution of salts of Adrenaline, Penicillin, Sterilized surgical ligature and
Surgical suture, Bacteriophages, etc.
Non- biological drugs: Drugs, which are obtained by synthesis or semi synthesis, are termed as
non- biological drugs, e.g. Paracetamol, Aspirin, Diclofenac, Metronidazole, Ciprofloxacin, etc.
Nature of drugs: Drugs are chemical substances. All of the drugs are either weakly acidic for
examples aspirin, diclofenac, etc or weakly basic for example, morphine, diazepam, etc.
According to physical nature drugs may exist as solid, liquid or gaseous state.
Examples of acidic and basic drugs:
Acidic drug: {ABCD} Basic drug: {DIPA}
 Aspirin  Digoxin
 Barbiturate  Isoprenaline-I
 Cloxacillin  Penicillin
 Diazepam  Atropine
 Diclofenac

Brand name: The name that is privately owned by a manufacturer or distributor and used to
distinguish them from competitor’s product is called brand name. Several companies may make
the same generic medicine, each with their own brand name. Paracetamol/Acetaminophen is a
generic name, there are several companies that make this with brand names such as Sinapol,
Tamen, Panadol, Calpol, Napa, etc. The IUPAC name of Paracetamol is N-(4-hydroxyphenyl)
acetamide.
Chemical name: A name used by the organic chemist to indicate the chemical structure of the
drug is called chemical name, e.g. N-(4-hydroxyphenyl) Acetamide is the chemical name of
Paracetamol, 2-acetoxybenzoic acid is the chemical name of Acetyl salicyclic acid.
Generic name: The established, nonproprietary, or common name of the active drug in a drug
product is known as the generic name. Each medicine (drug) has an approved generic name, e.g.
Acetaminophen, Acetylsalicylic acid (Aspirin), Diazepam, etc.
INN: INN means International Nonproprietary Names (INN). These names facilitate the
identification of pharmaceutical substances or active pharmaceutical ingredients. Each INN is a
unique name that is globally recognized and is public property. A nonproprietary name is also
known as a generic name. The INN system was initiated in 1950 by the World Health Assembly
and began operating in 1953. The INNs are selected by the World Health Organization on the
advice of experts from the WHO Expert Advisory Panel on the International Pharmacopoeia and

8
Pharmaceutical Preparations. INN system provides health professionals with a unique and
universally available designated name to identify each pharmaceutical substance. INNs are not
selected for herbal substances (vegetable drugs) for homoeopathic products, e.g. Heroin
(diacetylmorphine), Bardoxolone, Edoxaban, Ramelteon, Salbutamol, etc.

Complementary and Alternative medicines

Traditional medicines: Traditional medicine (also known as indigenous or folk medicine)

comprises medical aspects of traditional knowledge that developed over generations within
various societies before the era of modern medicine. It includes herbal medicines, Ayurveda
medicines, Unani medicines, Siddha medicines, Ancient Iranian medicines, Islamic medicines,
traditional Chinese medicines, traditional Korean medicines, traditional African medicines, and
other traditional medical knowledge practices all over the world.
The World Health Organization (WHO) defines traditional medicine as "the sum total of the
knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to
different cultures, whether explicable or not, used in the maintenance of health as well as in the
prevention, diagnosis, improvement or treatment of physical and mental illness."
Ayurveda medicines, Chinese, Homeopathy, Naturopathy, etc. are commonly known as
Complementary and Alternative medicines (CAM) in western countries. Among these systems
Ayurvedic, Unani and Homeopathic system of medicines are popularly practiced in south-asian
regions, including Bangladesh, Pakistan, India.
Herbal medicines: Herbal medicines include herbs, herbal materials, herbal preparations and
finished herbal products that contain as active ingredients parts of plants, or other plant materials,
or combinations.
Herbs: Crude plant material such as leaves, flowers, fruit, seed, stems, wood, bark, roots,
rhizomes or other plant parts, which may be entire, fragmented or powdered.
Herbal materials: In addition to herbs, fresh juices, gums, fixed oils, essential oils, resins and
dry powders of herbs are considered as herbal materials. In some countries, these materials may
be processed by various local procedures, such as steaming, roasting, or stir-baking with honey,
alcoholic beverages or other materials.
Herbal preparations: The basis for finished herbal products may include comminuted or
powdered herbal materials, or extracts, tinctures and fatty oils of herbal materials. They are
produced by extraction, fractionation, purification, concentration, or other physical or biological
processes. They also include preparations made by steeping or heating herbal materials in
alcoholic beverages and/or honey, or in other materials.
Finished herbal products: Herbal preparations are made from one or more herbs. If more than
one herb is used, the term mixture herbal product can also be used. Finished herbal products and
mixture herbal products may contain excipients in addition to the active ingredients. However,
finished products or mixture products to which chemically defined active substances have been

9
added, including synthetic compounds and/or isolated constituents from herbal materials, are not
considered to be herbal.
Forms of herbal and traditional medicines:
There are many forms of herbal and traditional medicines in which herbs preparations can be
administered, such as:
1. Tinctures: A tincture is typically an alcoholic extract of plant or animal material or solution
of such, or of a low volatility substance (such as iodine and mercurochrome). To qualify as
an alcoholic tincture, the extract should have an ethanol percentage of at least 25–60% (50–
120 US proof).
2. Herbal wine and elixirs: These are alcoholic extract of herbs; usually with an ethanol
percentage of 12-38%. Herbal wine is a maceration of herbs in wine, while an elixir is a
maceration of herbs in spirit (e.g. vodka, grappa, etc.)
3. Tisanes: Hot water extracts of herbs, such as chamomile.
4. Decoctions: Long-term boiled extract of usually roots or bark.
5. Macerates: Cold infusion of plants with high mucilage-content such as sage, thyme, etc.
plants are chopped and added to cold water. They are then left to stand for 7 to 12 hours
(depending on herb used). For most macerates 10 hours is used.
6. Vinegars: Prepared in the same way as tinctures, except using a solution of acetic acid as the
solvent.
7. Syrups: Extracts of herbs made with syrup or honey. For this usually 65 parts of sugar are
mixed with 35 parts of water and herb. The whole mixture is then boiled and macerated for
three weeks.
8. Extracts: These include liquid extracts, dry extracts and nebulisates. Liquid extracts are
liquids with a lower ethanol percentage than tinctures. They can be made by vacuum
distilling tinctures. Dry extracts are extracts of plant material which are evaporated into a dry
mass. They can then be further refined to a capsule or tablet. A nebulisate is a dry extracts
created by freeze-drying.
9. Inhalation: Inhalation as in aromatherapy that can be used as a mood changing treatment to
fight a sinus infection or cough, or to cleanse the skin on a deeper level.
10. Herbal paste: Fresh herbal pastes are applied onto the skin for soothing effect.
11. Pill/tablets: Formulation by mixing with suitable excipients. Many herbal tablet/pills are
available in the market.
12. Herbal capsule: Recently, a number of herbal drugs are formulated in capsule forms.

10
 Chapter- Two

Physiology and Anatomy

Physiology is the study of the function of living things, including processes such as nutrition,
movement, and reproduction. Anatomy is a study of structure or internal workings of something.
HUMAN PHYSIOLOGY: In human physiology, we attempt to explain the specific
characteristics and mechanisms of the human body that make it a living being.
There have 4 types of human physiology:
 Cell physiology: This is the cornerstone of human physiology; it is the study of the
functions of cells.

 Special physiology: This is the study of the functions of special organs. For example,
renal physiology is the study of kidney function.

 Systemic physiology: It includes all aspects of the function of the body system, such as
cardiovascular physiology, respiratory physiology, reproductive physiology etc.

 Pathophysiology: It is the study of the effects of diseases on organ or system functions.

Cell

Cell is the structural and functional unit of living being. Human body is built up by various types
of cells. The cells vary in size and shape. The size of the cells varies from 5-50 nanometers. A
mature ovum is the largest cell (130nm). A human cell mainly composed of a cell membrane,
nucleolus and cytoplasm.

Cell membrane: The cell membrane is tough elastic membrane that limits the protoplasmic
contents. It is about 7.5 to 10 nm in thickness.

Functions:

 It forms the boundary of cell.

 It maintain shape of a cell.
 It limits the protoplasmic contents within the cell.
 It controls the passage of all substances into or out of the cell.
 It acts as a sensory surface.

11
Mitochondria: Mitochondria are membranous organelles having greater metabolic significance.
It produces ATP so it is called power house of cell.

Functions:

 It is responsible for ATP production.

 It is the chief sites for Krebs’s cycle.
 Concerned with synthesis of DNA and RNA.

Nucleus: The nucleus is a rounded or elongated or spherical structure of cell which is associated’
with charring genetic information.

Functions:

 Vault of genetic information.

 Essential for biosynthetic events.
 Takes part in cell divisions.

Endoplasmic reticulum: An extensive network of membrane-enclosed tubules in the cytoplasm

of cells which is responsible for metabolic function.

Functions:

Smooth ER Rough ER

Associated with  Protein synthesis

 Provides a system for transport of newly
 CHO metabolism
 Cholesterol synthesis synthesis protein
 Lipid synthesis

Membrane transport

It is the bio- physio-chemical process by which different substances are transported through the
cell membrane from inside to outside or vice versa in our body.
Micromolecule: A molecule of relatively low molecular weight. Monomers are considered a
micromolecule that can be linked together to form polymer (which is a macromolecule).
Inorganic compounds like water and minerals are examples of micro molecules.
Macromolecule: A Macromolecule is a very large molecule commonly created by some form of
polymerization. In biochemistry, the term is applied to the four conventional biopolymers such
as nucleic acids, proteins, carbohydrates, and lipids.

12
Active transport: The movement of substance across the cell membrane against the
concentration gradient with active expenditure of energy by the help of carrier is called active
transport.
The energy derived from ATP and the carriers are present in the cell membrane.
Passive transport: The movement of substance across the cell membrane along the
concentration gradient from higher to lower is called Passive transport.
Exocytosis: The process by which cells release macromolecules to the exterior. Hormone,
enzyme, proteins are released by this process.
Endocytosis: The process by which cells take up macromolecules. It is of two types-
 Pinocytosis- applied for liquid substances. Protein and vitamins enter by this process.
 Phagocytosis- applied for microscopically visible substances as bacteria, dead cell etc.

Body fluid

Water of the body together with its dissolved solute is called body fluid. Most of the cellular
reaction occurs in the fluid media. Water is the essential constituents of the body fluid and
constitute about 57% of body weight in 70 kg adult male and 51% in adult female. In new born it
is about 75%.
Types of body fluid Body fluid compartment:
Basically there are two types of body fluid compartment.
 Intracellular fluid compartment: It is the sum total of the fluid content of all cells of
the body. It is about 28 liters (40%).
 Extracellular fluid compartment: It is the fluid outside of the cell. It is about 14 liters
(20%). The extracellular fluid in turn is divided into the-
 Interstitial fluid (5%)
 Blood plasma (15%)
There is another small compartment of fluid that is referred to as transcellular fluid. It is usually
considered to be a specialized type of extracellular fluid. It constitutes about 1 to 2 liters. This
compartments includes fluids-
 Synovial fluid
 Peritoneal fluid
 Pericardial fluid
 Intraocular fluid
 Cerebrospinal fluid

13
 Vitamins

Vitamins can be defined as organic substance that must be provided in small quantities in the diet
because they are not synthesized in the body of their rate of synthesis is inadequate for the
maintenance of the health.
Classification of vitamins
According to their solubility in the water and fat, vitamins are classified into two main groups.
A) Fat soluble vitamins
 Vitamin A (A1 and A2)
 Vitamin D (D1 and D2 )
 Vitamin E
 Vitamin K (K1, K2, and K3)
B) Water soluble vitamins
1. Vitamin B complex
 Thiamine (vit-B1)
 Riboflavin (vit-B2)
 Nicotinic acid: nicotinamide (vit-pp)
 Pyridoxine (vit-B6)
 Pantothenic acid (vit-B5 )
 Biotin (vit-H)
 Cyanocobalamin (vit-B12 )
 Folic acid (vit-B9)
2. Vitamin C (ascorbic acid)

Vitamin A

Maintain general health and vigor of epithelial cells. It is essential for formation of light sensitive
pigments in photoreceptor of retina. Beta carotene (provitamin of vitamin A, that naturally grow
in vegetables) act as an antioxidant.
Others name: retinol, anti-infective vitamin.
Vitamin A exits in two forms:
Animal food: As retinol
Vegetables: As β carotene
Types:
Vit-A1: retinol
Vit-A2: dehydro-retinol

14
 Sources of vitamin A:

Retinol Β-carotene
Liver, egg yolk, cod liver oil, milk, butter Dark green leafy vegetables, yellow and red
fruits, red palm oil.

Functions of vitamin A:
 Maintain normal epithelia
 Form retinal photochemical (rhodopsin)
 Anti-infective; enhance immune function
 Anti-carcinogenic
Indications:
 Acne ( retin A cream)
 Psoriasis
 Darier’s disease
Side effects:
 Dry skin
 Irritability
 Drowsiness
 Hepatomegaly
 Oedema
 Headache
 Fatigue

Vitamin D
 Vitamin D is pro-hormone.
 It is a member of steroid derivatives.
 The main precursor substance of vitamin D is cholesterol.
Vitamin D exists in two forms:
 Vit-D2 (ergocalciferol): plant origin.
 Vit-D3 (cholecalciferol): animal origin
Generated in the skin by photo-activation (u-v irradiation) of 7-dehydrocholestrol.
Dietary sources of Vitamin-D:
Fish liver oil e.g. cod liver oil
Halibut liver oil.

15
Fatty fish, egg yolk, liver, butter.
Functions of vitamin D:
Calcitriol {1, 25-(OH)2 D3} is the main active metabolites of vitamin D. There are three principle
sites of action of vitamin D (1) intestine (2) kidney and (3) bone. It maintains the calcium
homeostasis in the body.
Intestine increased Ca++& PO4 absorption by calcitriol.
Kidney decreased calcium and phosphate excretion by 25 (OH) D3 and 1, 25(OH)2 D3.
Bone increased calcium and phosphate excretion resorption by 1, 25-(OH)2D3.
Bone Formation may be increased by 24, 25-(OH)2D3.
Indications:
 Prevention and treatment of rickets
 Osteomalacia and osteoporosis
 Psoriasis
 Treatment of hypocalcaemia
 Muscle weakness and bone pain
Side effects:
 Polyuria
 Hypercalcemia
 Renal damage

Vitamin E

Vitamin E is a term used to refer to eight molecules, which are divided into two categories:
tocopherols and tocotrienols. Each category is further divided up into alpha (α), beta (β), gamma
(γ), and delta (δ) vitamers. The vitamer α-tocopherol is considered to be the ‘main’ vitamer, but
the gammas (γ-tocopherol and γ-tocotrienol) are also popular research topics, due to their
presence in the diet. Collectively, these compounds are called vitamin E. Vitamin E supplements
almost always contain α-tocopherol.
Sources:
 Fresh nuts
 Seed oil
 Green leafy vegetables and fruits
 Sunflower oil
 Cocoa butter
Indications:

16
  Sterility
 Recent abortion
 Progressive muscular dystrophy
 Cardiovascular disease
 Habitual abortion
 Pregnancy and lactation
 Antioxidant
 Enzymatic activity regulator
 Inhibit platelet coagulation
 Plays important role in eye and neurological function
Deficiency:
May cause oxidation of monosaturated fats, resulting in abnormal structure and function of
mitochondria, lysosomes, and plasma membranes.

Vitamin K

Acts as coenzymes that are essential for synthesis of several clotting factor by liver including
prothrombin.
Vitamin K is a fat soluble vitamin.
Types of vitamin-K
Vitamin-K1: phytomenadione (found in food)
Vitamin- K2: menaquinones (synthesized by intestinal flora)
Vitamin-K3: menadione
Sources:
 Animal (fish liver oil)
 Leafy vegetables
 Synthesis by bacteria flora in the colon
Indications:
 Warfarin overdose
 Chronic liver disease
 Obstructive jaundice
 Premature infants
Deficiency:
 Liver disease
 Hypo-prothrombinemia
 Hematuria and clotting factor deficiency

17
 Vitamin B complex

Vitamin B complex and their indications:

Vit- B1  Infantile beriberi

(thiamine)  Alcoholic neuritis
 Polyneuritis after infections disease
 Wenicke-korsakoff syndrome
 Anorexia nervosa
 Neuritis of pregnancy
 Chronic diarrhea
 Gastrointestinal hypotonia
Vit-B2  Glossitis
(riboflavin)  Cheilosis
 Angular stomatitis
 Sore throat
 Seborrheic dermatitis
 Photophobia
 Anemia
 Neuropathy

Vit-B3  For prophylaxis and treatment of pellagra

(niacin)  Hyper-cholesterolemia
 Hyper-triglyceridemia
 Vincent’s infections

Vit-B6
(pyridoxine)  INH induces peripheral neuritis
 Pregnancy radiation sickness
 Idiopathic sideroblastic anemia
 Convulsion in infants
Vit-B12  Pernicious anemia
(cyanocobalamin)  Trigeminal neuralgia
 Neuropathy
 Macrocytic anemia
 Tropical sprue
 Alcoholism
 Chronic impairment of liver parenchyma
Folic acid  Megaloblastic anemia
 Malabsorption syndrome
 Tropical sprue

18
 Vitamin-C

Promotes protein synthesis including laying down of collagen in formation of connective tissue.
It works with antibodies and promotes wound healing.
Sources of vitamin C:
 Amlaki
 Guavas
 Cabbage
 Tomato
 Cauliflower
Indications:
 Prevention and treatment of scurvy
 Treatment of wound and infections
 Urinary acidification
 Coryza
Side effects:
 Anemia
 Retardation of growth

Minerals

Minerals are inorganic substances required by the human body in very small amounts for its
growth and maintenance of its normal functions.

Functions of minerals:
 Minerals are essential constituent of all cells.
 Maintenance of osmotic pressure of body fluids.
 Needed in the formation of bones and teeth.
 They regulate the excitability of muscular and nervous system.
 Play an important role in water balance.
 Essential in the transport of gases.
Types of minerals:
Minerals are divided into two types-

19
Principal elements: These are found in the body in greater concentration. These include-
sodium, potassium, calcium, magnesium, phosphorus, sulphur and chloride.
Trace elements: These are found in the body in lower concentration. These include- chromium,
cobalt, copper, fluorine, iodine, iron, manganese, molybdenum, nickel, selenium, silicon,
vanadium, zinc.

Blood

Blood: Blood is a circulating tissue composed of fluid plasma and cells. Blood is a fluid that
transports oxygen and nutrients to the cells and carries away carbon dioxide and other waste
products. Technically, blood is a transport liquid pumped by the heart (or an equivalent structure)
to all parts of the body, after which it is returned to the heart to repeat the process. Blood is both
a tissue and a fluid. It is a tissue because it is a collection of similar specialized cells that serve
particular functions. These cells are suspended in a liquid matrix (plasma), which makes the
blood a fluid.
Blood is made of two parts:
1. Plasma (55%)
2. Blood corpuscles (45%)
There are three types of blood cell:
1. Red blood cells
2. White blood cells
3. Platelets
Properties of blood:
1. Blood volume : 5-6 litres
2. Normal reaction : Slightly alkaline
3. Specific gravity : 1.052 – 1.060
4. Viscosity : 4-5 times more viscous than water
5. Temperature : 36-38 degree celcius
6. Osmotic pressure : Average 25mm of Hg
7. Taste : Salty
8. Colour : Red, due to presence of haemoglobin inside RBC.

20
Functions of blood:
 Respiration: It transport respiratory O2 from lung to tissue and CO2 from tissue to lung.
 Transport of nutrients: It transport nutrients to tissue.
 Excretion: It carries metabolic waste products from tissue and excrete it through
excretory organs.
 Defensive function: WBC destroy foreign particles and microorganisms.
 Maintenance of water electrolytes balance: Fluid portion of blood is interchangeable with
intercellular fluid, thus it maintain water and electrolytes balance.
 Regulation of body temperature: With the help of water portion blood can regulate body
temperature.

Plasma

The fluid portion of blood is plasma. The watery, straw-colored, fluid portion of the lymph and
the blood in which the leukocytes, erythrocytes, and platelets are suspended.
Plasma protein: The protein that remains in plasma is known as plasma protein. Total normal
value- 6.0-8.0 g/dl.
Functions of plasma protein:
 It maintain colloidal osmotic pressure.
 It is essential for coagulation of blood.
 It acts as a buffer.
 It maintain ESR.
 It helps in transport of lipid hormone, Fe, Cu, drugs etc.
Source of plasma protein:
Exogenous: They are dietary source derived from first class protein (animal protein) or vegetable
protein.
Endogenous: Plasma proteins are produced in liver, reticuloendothelial system, tissue etc.

Haemopoesis

Haemopoiesis or haematopoiesis is the of process formation of new blood cellular components.

It has been estimated that in an adult human, approximately 1011 –1012 new blood cells are
produced daily in order to maintain steady state levels in the peripheral circulation. The mother
cells from which the progeny daughter blood cells are generated are known as haematopoietic
stem cells. In an embryo yolk sac is the main site of haemopoiesis whereas in human the basic
sites where haemopoiesis occurs are the bone marrow (femur and tibia in infants; pelvis,
cranium, vertebrae, and sternum of adults), liver, spleen and lymph nodes. In other vertebrates
haemapoiesis occurs in loose stroma of connective tissue of the gut, spleen, kidney or ovaries.

21
 Sites of Haemopoiesis in humans

Red Blood Corpuscle Erythrocyte

RBC is circular, bi-concave, non nucleated disc.

Normal count:
 Adult male - 4.5 - 5.5 million / cu mm of blood
 Adult female- 4.0 – 5.0 million / cu mm of blood
 Newborn – 6-7 million/cu mm of blood
Features of erythrocyte:
 Size and shape- bi-concave
 Thickness- at thickest point- 2-2.5 m
 Diameter- 7.5-7.8 m
 Volume- 90-95 cubic micrometers
 Life span- 120 days
Functions:
 RBC contains haemoglobin which carries O2 from lungs to tissue and CO2 from tissue to
the lungs.
 It contains antigen for blood group.
 By the buffering action of haemoglobin, it maintains acid base balance.

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 ESR (Erythrocyte sedimentation rate)

When the blood is mixed with a suitable anticoagulant and is made to stand vertically, red blood
corpuscle settle down to the bottom. The rate at which this sedimentation takes place is known as
erythrocyte sedimentation rate.
Normal value:
Westergren method
 Male – 0-6 mm in 1st hour
 Female- 0-12 mm in 1st hour
Wintrobe method
 Male- 0-12 mm in 1st hour
 Female- 0-18 mm in 1st hour
Importance of ESR:
 To see the prognosis of disease.
 To assay the condition of some chronic inflammatory disease, such as pulmonary
tuberculosis, pulmonary embolism, myocardial infraction, coronary thrombosis,
rheumatic arthritis, carcinoma.
 To see the therapeutic effects of drug.

ESR increases in ESR falls

Physiological condition Physiological condition
During menstruation In high altitude
During pregnancy In dehydration
Pathological condition Pathological condition
Multiple myeloma Hemochromatosis
Tuberculosis Polycythemia Vera
Rheumatic arthritis
Chronic inflammation
Malignancy
Coronary thrombosis
Haemorrhage
Toxemia of pregnancy
Other types of tissue necrosis

23
 Haemoglobin

Haemoglobin (Hb) is a complex protein-iron compound in the blood that carries oxygen and
carbon dioxide. Each erythrocyte contains 200 to 300 molecules of hemoglobin.
Normal value:
 Male- 14-18 gm/100 ml of blood
 Female- 12-16 gm/100ml of blood
 At birth- 23 gm/100ml of blood
Functions:
 It is essential for transport of O2 from lungs to tissue and CO2 from tissue to lungs.
 It is an important blood buffer.
 Various pigments of bile are derived from it.
 It reserves iron.

WBC (White blood corpuscle)

White blood corpuscle is the rounded colorless cells of blood which is responsible for body
immunity.
Features:
 Normal size- 10-12 micron
 Normal count- 4000-11000 /cu mm of blood
 Life span- few hours to few days
 Production- In bone marrow and lymphatic tissue
Functions of WBC:
 Phagocytosis- By this process WBC engulf bacteria and other foreign particles.
 Antibody formation- Lymphocyte produce antibody.
 Secretion of heparin- Basophil secrets heparin which prevent intra vascular clotting.
 Formation of fibroblast- Lymphocyte may be converted to fibroblast and helps in the
process of repair.
 Anti-histamine function- Eosinophil produce antihistamine 5-HT.
 Act as a scavenger- By removing of debris of dead tissue they do the job of scavenger.

Platelet or thrombocyte

Disk-shaped small blood cell which encourage the coagulation of blood.

24
Features:
 Diameter- 1-4 m
 Shaped- oval or rounded
 Nucleus- absent
 Normal count- 1.5-3.00 lac /cu mm of blood
 Life span-8-12 days
Functions:
 Plays an active role in blood clotting
 Initiate blood clotting
 Repair capillary endothelium

Haemostasis

Haemostasis means prevention of blood loss or arrest of bleeding. The termination of bleeding
by natural physiological or artificial process is called haemostasis (surgical). It consists of-
 Vasoconstriction
 Platelet aggregation
 Thrombin and fibrin synthesis
Coagulation of blood:
The conversion of blood from a free-flowing liquid to a semisolid gel/mass due to complex
actions of various coagulation factors is called coagulation of blood.
Blood coagulation factors:
Factor Synonym
Factor I Fibrinogen
Factor II Prothrombin
Factor III Tissue thromboplastic
Factor IV Calcium ions
Factor V Proaccelerin or labile factors
Factor VII Proconvertin or stable factor
Factor VIII Antihemophilic factor, antihemophilic globulin
Factor IX Plasma thromboplastin component (PTC), Christmas factor
Factor X Stuart factor
Factor XI Plasma thromboplastin antecedent (PTA), antihaemophilic factor C
Factor XII Hageman factor or glass factor
Factor XIII Fibrin stabilizing factor or Laki-Lorand factor
Prekallikrein Fletcher factor

25
High molecular weight Fitzgerald
kininogen
Platelets

Pathway of blood coagulation:

 Intrinsic pathway- for internal haemorrhage
 Extrinsic pathway- for external haemorrhage

Intrinsic Pathway
The intrinsic pathway is activated by trauma inside the vascular system, and is activated by
platelets, exposed endothelium, chemicals, or collagen. This pathway is slower than the extrinsic
pathway, but more important. It involves factors XII, XI, IX, VIII.

Extrinsic Pathway
The extrinsic pathway is activated by external trauma that causes blood to escape from the
vascular system. This pathway is quicker than the intrinsic pathway. It involves factor VII.

26
 Blood group

Typing of human blood based on presence of antigen on the cell surface of RBC is known as
blood group.
Principle blood group system:
 ABO system- Based upon the group specific substances, agglutinogen present in RBC
membrane.
 Rh system- Based upon the presence or absence of Rh antigen in blood.
 M and N system- Used in determination of paternity.
Classical blood group:
ABO system of blood are called classical blood group.
Agglutinogen: It is a polysaccharide that is present in the cell membrane of RBC.
Agglutinin: The agglutinins are gamma globulins most of them are IgM and IgG are produced in
the blood in absence of corresponding agglutinogen in RBC cell membrane.
Agglutinogen &Agglutinin in ABO blood group:
Blood group Agglutinin in plasma Agglutinogen in RBC
A Beta (𝛽) A
B Alpha (𝛼) B
AB No AB
O Alpha (𝛼), Beta (𝛽) No

Universal receiver:
According to ABO blood group system group AB can receive moderate amount (200-300ml) of
blood from all other groups of ABO system. So it is known as universal receiver.
Universal donor:
According to ABO blood group system group O can donate moderate amount (200-300 ml) of
blood to all other groups of ABO system. So it is known as universal donor.

Cardiovascular system

The system responsible for blood circulation is known as cardiovascular system. It composed of
heart and vessels (artery and vein).

27
Circulation:
The process in which blood & lymph flow through a closed system of vessels is called
circulation.
There are three types of circulation:
1. Systemic circulation
2. Pulmonary circulation
3. Coronary circulation
Systemic circulation: Passage of blood from left ventricle tissue & from the tissue to the right
atrium is called systemic circulation.
Pulmonary circulation: Passage of blood from right ventricle to the lungs & from the lungs to
the left atrium is called pulmonary circulation.
Coronary circulation: Nutrients are not able to diffuse quickly from blood to supply all the
layers of cells heart wall. For the reason, the myocardium has its own network & blood vessels
called coronary circulation.
Importance of circulation:
 To supply oxygen, nutrition and other essential elements to tissue.
 To carry waste products.
 To prevent intravascular coagulation.
 Helps to maintain temperature.

The heart

The heart is a muscular organ in humans and other animals, which pumps blood through the
blood vessels of the circulatory system. Blood provides the body with oxygen and nutrients, as
well as assists in the removal of metabolic wastes. In humans, the heart is located between the
lungs, in the middle compartment of the chest.
Feature of the heart:
General
 Shape- Conical
 Size-12 cm from base to apex
 Weight- 300gm in male, 250gm in female.
External
 Apex- Formed by the left ventricle.
 Base- Mainly by left atrium
 Four chamber- Right atrium, Left atrium, Right ventricle, Left ventricle.

28
Three surfaces:
 Anterior or sternocostal- Formed by – Right atrium and right ventricle.
 Inferior- Formed by left ventricle (2/3rd ) and right ventricle (1/3rd )
 Left surface- Mostly by left ventricle.
Four border:
 Upper border- Formed by two atria.
 Inferior- Mainly by right ventricle.
 Right border- Right atrium
 Left- Mainly by left ventricle.
Groove:
Atrioventricular groove or Coronary sulcus
 Anterior part
 Posterior part
Interventricular groove
 Anterior
 Posterior
Internal features:
Two septum:
 Interventricular septum
 Interatrial septum
Four valves:
Two atrioventricular valves
 Bicuspid valve
 Tricuspid valve
Two semilunar valves
 Pulmonary valve
 Aortic valve
Three layers of the wall:
 Outer epicardium- composed of mesothelial cell.
 Middle- myocardium-consist of cardiac muscle.
 Inner-endocardium- lined by squamous epithelium.

29
 Figure: The heart

Cardiac output

The cardiac output is simply the amount of blood pumped by the heart per minute. Necessarily,
the cardiac output is the product of the heart rate, which is the number of beats per minute, and
the stroke volume, which is amount pumped per beat.
CO = HR X SV
Where, HR= heart rate
SV= stroke volume
The cardiac output is usually expressed in liters/minute. For someone weighing about 70kg (154
lbs), the cardiac output at rest is about 5 liters/minute. In this case, if the heart rate is 70
beats/min, the stroke volume would be a little more than 70 ml/beat.

30
 Pulse or heart rate

Pulse is the rhythmic dilation and elongation of arterial wall as a result of the intermittent
ejection of blood from heart; transmit as a wave to the periphery.
 Normal pulse rate- 60-90 / minute.
 Average- 72 minute.

Tachycardia
It means fast heart rate. It is increased heart rate above the normal physiological limit. Usually
above 100 beats per minute is called tachycardia.
Causes-
 Raised body temperature.
 Stimulation of heart by sympathetic nerve.
 Toxic condition of heart.

Bradycardia

The term bradycardia means a slow heart rate. Decreased heart rate below the lower normal
physiological limit, usually below 60 beats per minute is called bradycardia.
Causes-
Bradycardia can be caused by:

 Heart tissue damage related to aging

 Damage to heart tissues from heart disease or heart attack
 Heart disorder present at birth (congenital heart defect)
 Infection of heart tissue (myocarditis)
 A complication of heart surgery
 Underactive thyroid gland (hypothyroidism)
 Imbalance of chemicals in the blood, such as potassium or calcium
 Repeated disruption of breathing during sleep (obstructive sleep apnea)
 Inflammatory disease, such as rheumatic fever or lupus
 Medications, including some drugs for other heart rhythm disorders, high blood pressure and
psychosis

31
 Blood pressure

Blood pressure can be defined as the lateral pressure of blood on its wall while flowing through
it.
Normal range- Average
 Systolic- 120 mm of Hg.
 Diastolic- 80 mm of Hg.
Importance:
 It is essential for the flow of blood through the circulatory tube.
 It provides motive force for filtration at the capillary bed which is essential for-
 Tissue nutrition
 Formation of urine
 Formation of lymph
 For venous return
Types of blood pressure:
 Systolic pressure
 Diastolic pressure
 Pulse pressure
 Mean pressure

Systolic pressure

It is the maximum pressure during systole. It is about 100-140 mm of mercury. Average- 120
mm of mercury.
Significance:
 The extent of work done by heart is known from systolic pressure.
 The force with which the heart is working.
 It increases during excitement, exercise, meals etc.
 It decreases while sleep, rest etc.

Diastolic pressure

It is the minimum pressure during diastole. It is about 60-90 mm of mercury. Average 80 mm of

mercury.
Significance:
 The constant load against which the heart works is known from diastolic pressure.

32
  Increased diastolic pressure indicates that heart is approaching to failure.
 It is the index of peripheral resistance.

Pulse pressure
It is the difference between systolic and diastolic pressure. It is about 30-40 mm of mercury.
Significance:
 It indicates the cardiac output.

Mean pressure
It is average pressure persist in the circulation. It is the diastolic pressure plus one third of pulse
pressure. It is about 78-98 mm of Hg. Average- 96 mm of Hg.
Significance:
 Increased mean pressure causes hypertension.

Respiratory system

The system is responsible for respiration is called respiratory system.

Respiratory tract: The passage responsible for air flow for respiration.

Divisions:

Upper respiratory tract: From nose (anterior flares) to the ‘vocal fold. It consists of-

 Nose
 Nasopharynx
 Oropharynx
 Larynx up to vocal folds

Lower respiratory tract: From vocal folds to the alveoli of the lungs. It consists of-

 Larynx below the vocal folds

 Trachea
 Two bronchi
 Bronchioles
 Alveolar duct
 Atria
 Air sac
 Alveoli

33
Functions of lung:

 Respiratory function
 Exchange of gases
 Non respiratory function
 Excretion- Lungs excrete volatile substances like ammonia, ketone body etc.
 Maintenance of acid base balance- This is done by adjusting of CO2 elimination.
 Maintenance of temperature balance- By evaporating water.
 Maintenance of blood circulation.

Respiration

Respiration is a physiological process which means the transport of oxygen from atmosphere to
the body cell for oxidation.

Phases of respiration:

Respiration has two phases-

Inspiration: It means intake of air in to lungs. Its duration is about 2 second.

Expiration: It means output of air from lungs. Its duration is about 3 seconds.

Rate of respiration:

Respiration rate vary according to age-

 At birth- 14-60 / min

 First year- 25-35 / min
 Adult male- 10-18 / min
 Adult female- 10-18 / min

34
 Transport of respiratory gases

Transport of oxygen:

It can be described in four steps

 Diffusion of O2 from alveolar air into pulmonary.

 Transport of O2 in the blood (in oxyhaemoglobin form and as solution).
 Diffusion of O2 from blood to tissue interstitial fluid.
 Diffusion of O2 from tissue interstitial fluid into cell.

Transport of carbon dioxide:

It can be described in four steps

 Diffusion of CO2 from cell into interstitial fluid.

 Diffusion of CO2 from cell into interstitial fluid to blood.
 Transport of CO2 in the blood (as carboxyhaemoglobin, bicarbonate and solution).
 Diffusion of CO2 from blood into alveoli of lung.

Digestive system

Digestive system: The system is responsible for digestion and absorption of nutritive substances.
The gastrointestinal system is the portal through which nutritive substances, vitamins, minerals,
and fluids enter the body. Proteins, fats, and complex carbohydrates are broken down into
absorbable units (digested). The products of digestion and the vitamins, minerals, and water
cross the mucosa and enter the lymph or the blood (absorption).
Digestion: Digestion may be defined as a physiological process by which complex food particles
are broken down into simple form, suitable for absorption and subsequent utilization.

Importance of digestion:

 Supply energy to the body for activity.

 For the growth of the body.
 For the repair of wear and tear.
 For the reproduction and lactation.

Absorption: Absorption is the process by which the end products of digestion pass through the
intestinal epithelium and enter the blood stream.

Parts of digestive system:

35
Digestive Tract

 Mouth or buccal cavity with tongue.

 Oropharynx.
 Stomach.
 Small intestine: Duodenum, Jejunum and Ileum.
 Large intestine: Caecum, Ascending colon, Descending colon, Sigmoid colon, Rectum,
and Anal canal.

Accessory parts

 Teeth
 Salivary glands: Parotid, Submandibular, Sublingual
 Liver
 Gall bladder
 Pancreas
 Other digestive glands in the wall of the digestive tract.

Alimentary tract: Extend from mouth to anus with their associated glands.

Gastrointestinal tract (GIT): Extend from stomach to anus.

Figure: Digestive system

Functions of digestive tract:

Nutritive functions:

 Ingestion of food.
 Digestion of food.
 Absorption of H2O, vitamins, salt and end products of digestion.
 Regulation of blood sugar level.
36
Secretory function:

 Secretion of various digestive juice.

Mechanical function:

 Helps in movement of food through it.

Maintaining function:

 Regulation of acid base balance.

 Regulation of water balance.

Saliva
Saliva is a viscous, colorless, opalescent fluid which is secreted by the three pairs of salivary
glands.

Secretion: It is secreted from salivary glands. Salivary glands are mixed gland. There are mainly
three pairs of salivary glands-

 Parotid glands: Parotid glands secret entirely the serous type, containing ptyalin (an
alpha-amylase).
 Submaxillary or submandibular glands: Secrete both the serous type and mucous.
 Sublingual glands: Secrete both the serous types and mucous.
 Buccal glands: There are small accessory buccal glands that secrete a small quantity of
saliva.

Functions of saliva:

 It keeps the mouth moist and helps in speech.

 It facilitates swallowing.
 It helps in preparing food staffs into a bolus, suitable for digestion.
 It dilutes hot and irritant food, thus prevents injury of the mucous membrane.
 Saliva also acts as a lubricant.
 Helps in taking the sensation of taste.
 Helps in water balance.
 Due to the presence of HCO3 and PO4 in saliva it acts as buffer.

37
 Gastric juice

Gastric juices are secreted from different types of cells present in stomach.

There are three types of gland present in the stomach.

Cardiac gland: It contains mainly mucous secreting cells.

Glands of body and fundus of stomach (Gastric glands or oxyntic glands):

 Mucous neck cell: Secrete mainly mucus but also some pepsinogen.
 Peptic or chief or zymogenic cell: Secrete large quantities of pepsinogen, gastric renin.
 Oxyntic or parietal cell: Secrete HCl and intrinsic factor of castle.
 Enterochromaffin cell: Secrete gastrin and serotonin.

Pyloric glands: Secrete mucin and lamina hormone gastrin.

Functions of gastric juice:

 The enzyme pepsinogen helps in protein digestion.

 Renin helps in milk digestion.
 Gastric lipase digests fat to some extent.
 Gastric HCl converts inactive pepsinogen into active pepsin.
 Gastric HCl acts as an antiseptic agent against bacteria.
 Gastric HCl causes hydrolysis of all the food staffs.
 It converts collagens protein into gelatin.
 Maintains acid base regulation.
 The intrinsic factor of gastric juice helps absorption of extrinsic factor (absorb Vit-B12)
essential for maturation of RBC.

Pancreatic juice

Pancreatic juice is a liquid secreted by the pancreas, which contains a variety of enzymes,
including trypsinogen, chymotrypsinogen, elastase, carboxypeptidase, pancreatic lipase,
nucleases and amylase. The pancreas is located in the visceral region, and is a major part of the
digestive system required for proper digestion and subsequent assimilation of macronutrient
substances required for living.

38
Functions of pancreatic juice:

 Digestive action: Due to the presence of high concentration of different enzymes,

pancreatic juice digests all three types of food-proteins, carbohydrates and fats.
 Neutralizing action: Pancreatic juice contains large quantities of HCO3, which plays an
important role in neutralizing the acid chime emptied by the stomach into the duodenum.

Bile

Bile is a bitter, yellow-green secretion of the liver, stored in the gallbladder and play an
important role in digestion.

Functions of bile:

 Digestive function: Bile helps in the digestion of fat and to a lesser extent of proteins and
carbohydrates with the help of bile salt which acts in the following way-
 By reducing surface tension
 By activating the action of lipase
 By solvent action.
 Absorption function: With the help of bile salts, bile help in the absorption of fat and
other substances like fat soluble vitamins, iron, calcium etc.
 Mucin of bile acts as buffer and lubricant.

Liver
It is the largest solid gland of the body, situated within abdominal cavity and play an important
role in digestion and metabolism.

39
Functions of the liver:

 Nutrient and vitamin metabolism.

 Storage function- Glycogen, vitamin, iron.
 Production of bile, which helps carry away waste and break down fats in the small
intestine during digestion
 Production of certain proteins for blood plasma
 Production of cholesterol and special proteins to help carry fats through the body
 Store and release glucose as needed
 Processing of hemoglobin for use of its iron content (the liver stores iron)
 Conversion of harmful ammonia to urea (urea is one of the end products of protein
metabolism that is excreted in the urine)
 Clearing the blood of drugs and other harmful substances
 Regulating blood clotting
 Resisting infections by producing immune factors and removing bacteria from the
bloodstream
 Clearance of bilirubin (if there is a buildup of bilirubin, the skin and eyes turn yellow)

Metabolism

Metabolism may be defined as a series of specific biochemical reaction occurring within living
organism, catalyzed by enzymes, coenzymes, co-factors and governed by hormones and
vitamins. It is the sum total of anabolism and catabolism.

Anabolism: The synthesis processes or the energy consuming process for conversion of simple
substances into the more complex compounds.

The reactions of anabolism are:

 Synthesis of glycogen from glucose (glycogenesis).

 Lipid synthesis (lipogenesis).
 Protein synthesis.
 Ketone body synthesis.
 Urea synthesis.
 Cholesterol synthesis

Catabolism: The breakdown processes or the processes that convert bigger molecules into
smaller form for the supply of energy.

The reactions of catabolism are:

 Break down of glycogen into glucose-glycogenolysis.

40
  Breakdown of glucose-glycolysis.
 Break down of lipid-lipolysis.
 Protein catabolism.

Importance of metabolism:

A part of energy produced by metabolism is stored and rest is utilized for-

 Protein synthesis and growth of the body.

 Muscular activities.
 Secretion of glands.
 Absorption of food from GIT.
 Other body activities.

Urinary system
The system responsible for production and excretion of the waste product of body is called
urinary system..

Parts of urinary system:

Organ Principal function

A pair of kidney Formation of urine

A pair of ureters Convey urine from kidney to bladder

A urinary bladder Temporary reservoir of urine

Urethra Excrete urine from bladder to exterior.

Parts of urinary system

41
Kidney: It is the principal organ of urinary system that produce urine. There are two kidneys in
human body. Kidney consist of two parts-

 Outer cortex
 Inner medulla

Contents of different parts of kidney:

Cortex is consist of- Medulla is consists of-

 Glomerulus  Loop of henle

 Bowman’s capsule  Collecting tubule
 Proximal convoluted tubule
 Distal convoluted tubule
 Collecting tubules
 Afferent and efferent arterioles
 Juxta glomerular apparatus

Functions of kidney:

 It maintains electrolyte balance.

 It maintains acid-base balance.
 It excretes ammonia urea and other waste products.
 It secrets erythropoietin, prostaglandin, renin etc.
 It maintains blood pressure by renin-angiotensin mechanism.
 It eliminates drug and various toxin from body.
 Converts vitamin-D into its active form.
 It helps in gluconeogenesis.

Nephron: It is the structural and functional unit of kidney. There are approximately 1.3 million
nephrons in each human kidney.

42
Parts of nephron:

Two major parts of the nephron are the renal corpuscle and the renal tubule. The corpuscle has
the glomerulus .Cleansing of the blood occurs in this part of the nephron. The glomerulus, which
is a tuft of very small blood vessels, has tiny holes that act as a filter. It allows water, wastes and
small materials to pass through. Larger particles and substances including cells and proteins are
not allowed to pass through this filter. The filtered fluid including wastes and other substances
then pass through a very small tube called the renal tubule. It is a continuous tube, which has
four major parts: the proximal tubule, descending loop, ascending loop and the distal tubule.

Functions of nephron:

 It filters blood.
 It secretes erythropoietin.
 Maintain blood pressure.
 Maintain water electrolyte balance.
 Maintain electrolyte balance.

Glomerular filtration: The filtration that occurs through the glomerular capillary is called
glomerular filtration.

Glomerular filtrate: The fluid that filters through the glomerulus into bowmen’s capsule is
called glomerular filtrate.

Glomerular filtration rate: The quantity of glomerular filtrate formed in each minute by all the
nephrons of both kidneys is known as glomerular filtration rate. Normal value- 125ml/ minute.

Renal/ plasma clearance: The rate at which different substances are cleared from the plasma via
the kidneys.

43
Plasma clearance= V × U/P

V= Urine volume

U= Urine concentration of substance

P= Plasma concentration.

Renal threshold: Concentration of a substance in plasma at which it begins to be excreted in the

urine. E.g. renal threshold of glucose is -180mg/100ml.

Endocrinology
Endo = Internal and crinos = secretion

Endocrinology is a branch of medical science which deals with the study of different endocrine
glands of the body.

Endocrine gland: Means ductless gland which directly poured their secretion into the blood.
Secretion of gland is known as hormone.

Principal Endocrine glands are:

 Hypothalamus (neuroendocrine gland)

 Pituitary gland (master gland)
– Anterior pituitary gland
– Posterior pituitary gland
 Thyroid gland
 Parathyroid glands
 Adrenal glands
– Adrenal cortex
– Adrenal medulla
 Pancreas (Endocrine portion- Islets of Langerhans)
 Testis
 Ovaries
 Placenta (during pregnancy)

Functions of endocrine glands:

Endocrine glands secrete hormone, those are responsible for-

 Metabolism.
 Growth and development.
 Water and electrolyte balance.
 Development of sexual characteristics.

44
Name of important endocrine glands of the body:

Name Location Principle function of its secretion

Hypothalamus In the diencephalon of the Control secretion of other endocrine

brain. glands.

Anterior pituitary Lies in the base of the brain. Growth and development.

Posterior pituitary Lies in the base of the brain. Regulate water balance.

Adrenal At the upper pole of kidney. Maintain electrolyte balance

Thyroid At the front of the neck. Helps in body metabolism.

Parathyroid Near thyroid gland. Maintain calcium balance.

Pancreas (Islets of In abdominal cavity. Maintain glucose level of blood.

Langerhans)

Ovary It lies pelvis of female. Responsible for female

reproduction.

Testis Within the scrotum of male. Responsible for male reproduction.

Placenta In gravid uterus Responsible for fetal growth.

Hormone

Hormone is a chemical substance that is secreted into the internal body fluid by one cell or group
of cells and exerts a physiological control effect on other cells of the body.
Classification of hormone:
I. Based on chemical nature:
i. Proteins or polypeptides hormone:
a. Anterior pituitary:
1. Growth hormone
2. Adrenocorticotropic
3. Thyroid stimulating
4. Follicle stimulating.
5. Luteinizing hormone
b. Posterior pituitary:
- Antidiuretic hormone
- Oxytocin

45
 c. Pancreas:
-Insulin
-Glucagon
d. Parathyroid gland:
-Parathyroid hormone etc.
ii. Steroid hormone:
a. Adrenal cortex
-Cortisol
-Aldosterone
b. Ovaries
-Estrogen
-Progesterone
c. Testes
-Testosterone
d. Placenta
-Estrogen
-Progesterone
iii. Derivatives of the amino acid tyrosine:
a. Thyroid
-Thyroxine
-Triiodothyronine
b. Adrenal medulla
-Epinephrine
-Norepinephrine
There are no known polysaccharide or nucleic acid hormones.
II. Based on site of action
i. General hormone: e.g. Growth hormone, Thyroid hormone, Insulin.
ii. Local hormone: e.g. Local hormone of GI tract.
iii. Trophic hormone: e.g. TSH, ACTH, LH etc.
Function of hormone:
 Metabolism: e.g. Insulin, Glucagon, Thyroid, Cortisol.
 Growth: Growth hormone.
 Reproduction: e.g. testosterone, oestrogen.
 Combating emergency: e.g. Adrenalin and Noradrenalin.

Nervous system

Nervous system is the important organization which control and integrates the different body
function and maintain internal environment.

46
Components of nervous system:
 Central processing part or brain
 Sensory portion – which carries impulses
 Motor portion – which carries the orders for action
Function of nervous system:
 Collection of impulses from various parts of the body.
 Processing of impulses.
 Preparation of order according to impulse.
 Distribution of orders (efferent) to various parts of body.
 Creation of mental emotion.
Classification of nervous system:
Nervous system

Central nervous system peripheral nervous system

Brain Spinal cord

Fore brain Mid brain Hind brain

Somatic Autonomic

Spinal Cranial

Sympathetic Parasympathetic

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 Figure: Nervous system

Neuron
Neuron is the structural and functional unit of the nervous system. A nerve cell with its all
processes is known as neurons. Neurons carry messages throughout the body, including sensory
information from external stimuli and signals from the brain to different muscle groups in the
body. In order to understand exactly how a neuron works, it is important to look at each
individual part of the neuron. The unique structures of the neuron allow it to receive and transmit
signals to other neurons as well as other types of cells.

Dendrites

Dendrites are treelike extensions at the beginning of a neuron that help increase the surface area
of the cell body. These tiny protrusions receive information from other neurons and transmit
electrical stimulation to the soma. Dendrites are also covered with synapses.

Soma

The soma or cell body is where the signals from the dendrites are joined and passed on. The
soma and the nucleus do not play an active role in the transmission of the neural signal. Instead,
these two structures serve to maintain the cell and keep the neuron functional.

48
Axon

The axon is the elongated fiber that extends from the cell body to the terminal endings and
transmits the neural signal. The larger the diameter of the axon, the faster it transmits
information. Some axons are covered with a fatty substance called myelin that acts as an
insulator. These myelinated axons transmit information much faster than other neurons.

Figure: The Neuron

There are three types of neurons in the body.

1: Sensory (Afferent) neuron: A neuron that detects changes in the external or internal
environment and sends information about these changes to the CNS. (E.g. rods and cones, touch
receptors). They usually have long dendrites and relatively short axons.
2: Interneurons or association neurons: A neuron located entirely within the CNS in which
they form the connecting link between the afferent and efferent neurons. They have short
dendrites and may have either a short or long axon.
3: Motor (Efferent) neuron: A neuron located within the CNS that controls the contraction of a
muscle or the section of a gland. They usually have short dendrites and long axons.

Synapse

Synapse: It is the point in the nervous system where two neurons are in contact with each other.
Function of synapses:
 Conduction or transmission of impulses.
 Integration of impulses.
 Formation of reflex arc.

49
  Acts as a connection spot in neural chain.

Figure: The synapse

Neurotransmitter

Chemicals that modify or result in the transmission of nerve impulses between synapses are
called neurotransmitter. These are highly active chemical agents released at the nerve ending and
transmit impulses from nerve to nerve or from nerve to effector tissue.
Some neurotransmitter
Excitatory Inhibitory Both excitatory and inhibitory

Acetylcholine Dopamine 5-HT (Hydroxytryptamine)

Adrenaline Glycine Histamine
Noradrenaline Taurine Prostaglandin
Glutamate Alanine Nor-epinephrine
GABA
Serotonin

Male reproductive system

The organs and tissues those are responsible for male reproduction collectively known as male
reproductive system.
Organs of male reproductive system:
Primary male sex organ
 Testes
Secondary sex organ (accessory sex organ)
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  Penis
 Scrotum
 Prostate
 Seminal vesicle
 Urethra
 Epididymis
 Vas deference
 Ejaculatory duct
 Bulbo urethral gland
Functions of different organs of male reproductive system:
Parts Function
Testes  Production of spermatozoa.
 Secretion of hormone- testosterone.
Scrotum  It covers the testis.
 It protects the testis.
Penis  It is the copulatory organ of male.
Prostate  Secretion of prostatic fluid.
Epididymis  Carries sperm from the seminiferous tubules of the testes to
the vas deferens.
 It acts as a reservoir of spermatozoa.
Seminal vesicle  Its secretion forms a large part of seminal fluid.
 Its secretion contains fructose which provides nutrition to
spermatozoa.

Ejaculatory duct  Transmit spermatozoa and seminal bulk to urethra during

orgasm.

Male reproductive hormones:

Gland Hormone
Hypothalamic Gonadotropin releasing hormone (Gn RH).
Anterior pituitary Luteinizing hormone-it stimuli the secretion of testosterone.
Follicle stimulating hormone-stimulus spermatogenesis.
Testes Testosterone
Inhibin

Function of testosterone:
 Helps in growth of accessory sex organ.
 Helps in development of secondary sex characteristics.
 Facilities spermatogenesis.

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  Increase metabolism.
 Helps in development of bones and muscles.
Semen: Semen can be defined as a fluid formed by the secretion from testis, seminal vesicle,
prostate and bulbo-urethral gland which passes out through male urethra during orgasm.
Sterility: It means loss of reproductive capacity.
Causes-
 Failure of erection of penis.
 Failure to discharge sufficient quantity of semen.
 Less sperm count.
 Presence of more than 20% abnormal sperm in semen.
 Impaired movement of sperm.
Impotency: Inability to perform sexual intercourse (i,e. failure to excretion of penis).
Causes-
 Malnutrition
 Mental inability
 Genital infection
Gynecomastia: Abnormal enlargement of one or both breasts in male is called gynecomastia.
Causes-
 Tumor in pituitary, testis, etc. (produce female hormone).
 Drug containing female reproductive hormone compounds.
 Liver disorder.

Female reproductive system

The organs and tissues those are responsible for female reproduction collectively known as
female reproductive system.
Parts of female reproductive system:
Primary female genital organ
 Ovary
Secondary female genital organ (accessory)
 Fallopian tube
 Uterus
 Vagina
 Bartholin gland

52
  Valve
 Breast
 Placenta
Organ Function
Ovary  Production of ovum.
 Production female sex hormones-oestrogen, progesterone.
Uterus  Harbor fetus.
 Show the signs of menstrual cycle.
Fallopian tube  Convey ovum from to uterus.
 Fertilization of ovum occurs within fallopian tube.

Vagina  Route of copulation.

 Route of parturition.
 Route of menstruation.
Placenta  Transport of oxygen from mother to foetus.
 Transport of carbon dioxide from to foetus mother.
 Transport nutrient, hormones vitamins from mother to foetus.
 Secretion of hormones.
 Act a barrier and prevent many harmful substances from
reaching foetus.

Breast Secrets milk for nutrition of baby.

Female reproductive hormones:

Gland Hormone
Hypothalamic Gonadotropin releasing hormone (GnRH)
Anterior pituitary Luteinizing hormone- it stimuli the secretion
of female hormones.
Follicle stimulating hormone- stimulus
ovulation
Prolactin-development of breast for lactation.
Posterior pituitary Oxytocin-contraction of uterus during labor,
milk secretion from breast.
Ovary Estrogen
Progesterone
Relaxin (relax pelvis ligament during labor
thus helps in dilation of cervix)
Placenta Estrogen
Progesterone
Chorionic gonadotropin hormone (stimulates
ovary to secrete hormones)

53
 relaxin.

Functions of estrogen:
On ovary
 It has a stimulatory effect on follicular growth.
On fallopian tube
 Promotes motility.
 Stimulus tubular secretion.
On uterus
 Causes proliferation phase of endometrium.
 Increases size of uterus.
On vagina
 Development of epithelium.
On breast
 Development of stromal tissue.
 Development of ductile system.
 Deposition of fat.
Functions of progesterone:
On uterus
 Causes secretory phage of endometrium.
On fallopian tube
 Increase tubal secretion.
On breast:
 Promotes proliferation of lobule and alveoli.
 Prepared breast for lactation.
On vagina
 Increase secretion of vaginal epithelium.

54
 Ovulation

It is the process of expulsion of an ovum from the ovary on spontaneous rupture of a mature
follicle. It usually occurs on the fourteenth day after the first day of the last menstrual period.

Ovarian cycle

The periodical changes occur within ovary for the purpose of follicular maturation and ovulation
is known as ovarian cycle.
Phases of ovarian cycle-
 Follicular phases- In this phase follicular development and ovulation takes place. It lasts
for 14±1 days.
 Luteal phase- In this phase various changes in corpus luteum occurs.

Menstruation

Menstruation is the periodic discharge of blood containing tissue debris of endometrial shedding
through the vagina from the non pregnant uterus. The cyclic discharge of blood, unfertilized
ovum, mucous and certain other substances per vagina from uterus in the reproductive life of
female at an interval of 28 days is called menstruation. Average duration of menstruation is 4-7
days.
Menstrual cycle

The periodically recurrent series of changes occurring in the uterus and associated sex organs
(ovaries, cervix, and vagina) associated with menstruation and the intermenstrual period is
known as menstrual cycle. It also called as female monthly sexual cycle. The duration of the
cycle averages 28 days.
Significance of menstrual cycle:
 First, only a single ovum is normally released from the ovaries each month.
 Second, the uterine endometrium is prepared in advance for implantation of the fertilized
ovum at the required time of the month.
Stages of menstrual cycle:
Proliferative phase: It is also called oestrogenic phase. Duration is 8-10 days. Changes occurs
in this stage-
 Thickness of endometrium becomes 2-3 mm.
 Proliferation of epithelium.
 Growth of blood vessels.

55
  Enlargement of tubular glands.
Secretory phase: It is also called progesteronic phase. Its duration is 9-10 days. Changes occurs
in this stage-
 Further proliferation of stromal tissue.
 Endometrial thickness becomes 4-6 mm.
 Blood vessels become highly tortuous.
 Secretion of epithelial glands.
Menstrual phase: Also called bleeding phase. It occurs when fertilization does not take place.Its
duration is 5-7 days. Changes occurs in this stage-
 Necrosis of endometrium and blood vessels.
 Shedding of necrotic layer.
 Uterine contraction.
 Expulsion of necrosis tissues through vagina.

Menstruation during pregnancy

If fertilization does not occur, menstruation occurs at the 14 days after ovulation due to sudden
fall of blood estrogen and progesterone level.
But if fertilization and implantation occur, the trophoblastic cell of the placenta secretes large
quantities of chorionic gonadotropin which prevent the involution of corpus luteum. This corpus
luteum secretes large quantities of estrogen and progesterone which continue the growth of
endometrium and prevents the menstruation. So, menstruation does not occur during pregnancy.

56
 Placenta

It is an accessory female sex organ which forms at pregnancy to maintain a channel in between
mother and foetus.
The placenta is an important foetal membrane which acts as a temporary endocrine gland and
maintains a channel in between mother and foetus.
Hormones of placenta:
 Human chronic gonadotropin
 Estrogen
 Progesterone
 Somatotropin
 Relaxin
Functions:
 Transport of oxygen from mother to foetus.
 Transport of carbon di oxide from mother to foetus mother.
 Transport nutrient, hormones, vitamins etc from mother to foetus.
 Excretion of metabolic waste product from foetus.
 Secretion of hormones.
 Act a barrier and prevent many harmful substances reaching foetus.

Puberty: Means the onset of reproductive life.

Menarche: Means the onset of menstruation.
Menopause: Means the cessation of menstruation.
Amenorrhoea: It means the absence of menstruation.
Dysmenorrhea: It means painful or difficult menstruation.
Reproductive period: It is the life of female between menarche and menopause.
Danger period: From 9 to 17th days of menstruation or roughly the middle week of
menstruation.
Viable period: Gestational age of 24 weeks roughly 7 month is called viable period.
Abortion: Termination of pregnancy before the fetus become viable is called abortion.

57
Functions of organ system

Systems System organs Function

Endocrine Adrenal gland, pituitary gland, Provide communication
thymus, parathyroid gland, between cells of the body by
pancreas. release of hormones in to the
blood stream.
Nervous Brain, spinal cord, peripheral Provide communication
nerves between cells of the body
through the electrical signals
and release neurotransmitter
into gaps between the certain
cells.
Musculoskeletal Skeletal muscle, bones, Support the body
tendons, ligaments
Respiratory Lungs, pharynx, trachea Bring oxygen in to the body
bronchi and eliminate CO2 from the
body.
Gastrointestinal Mouth, esophagus, stomach, Break down the food and
large intestine, small intestine, absorb into the body
pancreas ,gall bladder ,liver
Cardiovascular Heart, blood vessel, blood Transport O2, CO2, nutrients
and waste products throughout
the body
Reproductive Reproductive tracts and Generate offspring
glands, gonads
Immune White blood cells, thymus Protect the body against
,lymph nodes, adenoids, pathogens
tonsils, spleen
Urinary Ureters, , bladder, kidney Filter the blood to regulate
acidity, blood volume and ion
concentrations; eliminate
wastes.
Integumentary skin Protect the body from the
external environment.

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 pH

pH: pH is the negative logarithm of hydrogen ion.

pH= − log [H+]
pH of different parts of a human body varies. The pH of different parts of body is
Blood: 7.35−7.45
Saliva: 5.5− 7.5
Gastric juice: 1.5− 3.5
Bile: 6− 8.5

Urine: 4.5 – 8.00

Tear: 7.4
Skin: 5.5

HCl: 1.2 – 1.4

59
 Chapter-Three

Chemistry

Chemistry: The branch of science that deals with identification of the substances of which
matter is composed; the investigation of their properties and the ways in which they interact,
combine, and change; and the use of these processes to form new substances.
Five branches:
There are five main branches of chemistry, each of which has many areas of study.
Analytical chemistry: Analytical chemistry uses qualitative and quantitative observation to
identify and measure the physical and chemical properties of substances. In a sense, all chemistry
is analytical.
Physical chemistry: Physical chemistry combines chemistry with physics. Physical chemistry
are study how matter and energy interact. Thermodynamics and quantum mechanics are two of
the important branches of physical chemistry.
Organic chemistry: Organic chemistry specifically studies compounds that contain the
element carbon. Carbon has many unique properties that allow it to form complex chemical
bonds and very large molecules. Organic chemistry is known as the “Chemistry of Life” because
all of the molecules that make up living tissue have carbon as part of their makeup.
Inorganic chemistry: Inorganic chemistry studies materials such as metals and gases that do not
have carbon as part of their makeup.
Biochemistry: Biochemistry is the study of chemical processes that occur within living
organisms.

Functional group and chemical bonding

Functional group and chemical bonding:

Functional group:
A functional group is a portion of a molecule that is classified group of bonds atoms. In organic
chemistry it is very common to see molecules comprised mainly of a carbon backbone with
functional groups attached to the chain.
Example: Alcohol= -OH
Aldehydes= -CHO
Ketone = -O-

60
Electron shell:

An electron shell is the outside part of an atom around the atomic nucleus. It is a group of atomic
orbitals with the same value of the principal quantum number n.
Each shell is subdivided into sub shells, which are made up orbital, each of which has electrons
with different angular momentum. Each orbital in a shell has a characteristic shape. Orbital has 4
shells.
The four shells are:

1. S(2)
2. P(6)
3. D(10)
4. F(14)

Orbit:

It is well defined circular path followed by revolving electron around the nucleus.

Orbital:

It is a region of space around the nucleus where the electron is most likely to be found.

Orbit Orbital
As postulated by Bohr, an orbit is a definite As postulate by wave nature of an electron, an
circular path at a definite distance from the orbital is a three-dimensional region around the
nucleus in which the electron revolve round the nucleus within which the probability of finding
nucleus. Orbits are designated by the capital an electron is maximum., Orbital’s are
letters K, L, M, N…. etc. designated by s, p, d… etc.
Orbits are circular in shape. Orbital’s have different shapes.
It represents the planer motion of the electron. It represents the three-dimensional motion of
the electro round the nucleus.
An orbit indicates an exact position of an An orbital does not specify the exact position
electron in an atom. of an electron in an atom.
The maximum number of electro in an orbit is An orbital cannot accommodate more than two
equal to 2n2, where n is the number of the electrons.
orbit.

61
Resonance:

Resonance or mesomerism is a way of describing delocalized electrons with molecules or

polyatomic ions where the bonding cannot be expressed by one single lewis structure. A
Molecule or ion with such delocalized electrons is represented by several contributing structures
or resonance.
Aromaticity:

First aromatic term used by august Wilhelm Hofmann in 1855. The term aromaticity is used to
describe a cyclic, planar molecule with a ring of resonance bonds that exhibits more stability
than other geometric or connective arrangements with the same set of atoms. Aromatic
molecules are very stable and do not easily break apart and react with other substances. Example:
benzene.

Functional group

Esters:

Esters are chemical compounds derived from an acid in which at least one –OH group replaced
by an -o- alkyl group. Usually, esters are derived from a carboxylic acid and an alcohol.

Carboxylic acid:

A carboxylic acid is an organic compound that contains a carboxyl group (COOH). The general
formula of a carboxylic acid is R-COOH, with referring to the rest of molecule.

Carboxylic acid composed of two functional groups:

1. Hydroxyl group
2. Carbonyl group

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 Formula: -COOH
Amides:

An amide is a compound with the functional group R-NH2. Most common are carboxamides, but
many other important types amide are known including phosphoramides and sulfonamides it’s
also regarded as derivatives of carboxylic acids in which the hydroxyl group has been replaced
by amine or ammonia. The lone pair of electrons on the nitrogen is delocalized into the carbonyl,
thus forming a partial double bond between N and the carbonyl atom.
Aldehydes:

An aldehydes or alkanal is an organic compound containing a functional group with the structure
–CHO, consisting of a carbonyl center (a carbon double bonded to oxygen) with the carbon atom
also bonded to hydrogen and to an R group. Functional group: -CHO
It contains formyl group. A formyl group is a part of molecule with the structure R-CHO
Ketons:

CH3-O-CH3
A ketone is an organic compound with the structure R-O-R, where R and R can be variety of
carbon containing substances. The ketone is the simple compounds that contain carbonyl group.

Acid and Base

According to Bronsted and Lowry theory, acids are defined as proton donors where bases are
defined as proton acceptors. A compound that can act as both a Bronsted acid and base together
is called amphoteric.

Strength of acid and base:

The strength of an acid and base refers to its ability or tendency to accept or to lose a proton. In
other words, the strengths of acids and bases depend on how much an acid or base ionizes in
solution. A strong acid is one that completely ionizes and gives proton. A strong base is one that
completely ionizes and accepts proton. Example of strong acid is HCl and weak acid is acetic
acid CH3COOH. Example of strong base is NaOH and weak base is NH4OH.

Electronegativity:

Electronegativity is a measure of the tendency of an atom to attract a bonding pair of electrons.

The Pauling scale is the most commonly used. Fluorine is the most electronegative atom is
assigned a value 4.0, and values range down to cesium and francium which are the least
electronegative 7.0.

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Heterolytic bond formation:
In chemistry, heterolysis or heterolytic fission (from Greek heteros,” different” and lusis,
“loosening”) involves cleavage of a chemical bond in a process where both of the electrons
involved in the original bond remain with only one of the fragment species. During heterolytic
bond cleavage in a neutral molecule, a cation and anion will be generated. Typically, the more
electronegative fragment will retain the pair of electrons.
Activation energy:
Activation energy is a term introduced by the Swedish scientist Svante Arrhenius to describe the
minimum energy which must be available to chemical system with potential reactants to result in
a chemical reaction. Activation energy may also be defined as the maximum energy required to
start a chemical reaction. The activation energy of a reaction usually is denoted by Ea and given
in units of kilo joules per mole or kilo calories per mole. For a chemical reaction to proceed at a
reasonable rate, there should exist an appreciable number of molecules with translational energy
equal to or greater than the activation energy.
Reaction kinetics:
Chemical kinetics is the study and discussion of chemical reactions with respect to reaction rates,
effect of various variables, re-arrangement of atoms formation of intermediates etc. There are
many topics to be discussed, and each of these topics is a tool for the chemical reaction kinetics.
Isotope kinetics effect:
Isotopic substitution is a useful technique for the probing of reaction mechanisms. The change of
an isotope may affect the reaction rate in a number of ways, providing clues to the pathway of
the reaction. The advantage of isotopic substitution is that this is the least disturbing structural
change that can be effected in a molecule.

Stereo chemical and conformational isomerism

Stereo chemical and conformational isomerism

Stereo chemical structure:
Stereochemistry, a subdisclipline of the chemistry, involves the study of the relative spatial
arrangement of atoms that from the structure of molecules and their manipulation. An important
branch of stereochemistry is the study of chiral molecules.
Stereochemistry is also known as 3D chemistry because the prefix “stereo “means three –
dimensionality”.

64
Chiral center:
A chiral center is defined as an atom in a molecule that is bonded to four different chemical
species, allowing for optical isomerism.

Optical activity:
Optical activity was first observed by the French physicist Biot Savart. He concluded that the
change in direction of plane light when it passed through certain substances was actually a
rotation of light and that it had a molecular basis. His work was supported by the
experimentation of Louis Pasteur observe the existence of two crystals that were mirror image in
tartaric acid found in wine.
Stereo electronic effects:
The stereoelectronic effect is the effect on molecular structures, physical properties and
reactivities due to the molecules' electronic structures, in particular the interaction between
atomic and/or molecular orbitals.

Carbon-carbon bond formation

Electrophiles:
A reagent which can accept an electron pair in a reaction is called an electrophile. The name
electrophile means “electron-loving” and indicates that it attacks regions of high electron density
(negative centres) in the substrate molecule. Electrophiles are electron-deficient. They may be
positive ions (including carbonium ions) or neutral molecules with electron-deficient centres.
Examples are H+, Cl+, Br+, I+, NO2+, R3C+, AICI3, BF3.
Electrophilic substitution reactions:
When a substitution reaction involves the attack by an electrophile, the reaction is referred to as
electrophilic reactions.
Nucleophiles:

65
A reagent which can donate an electron pair in a reaction is called a nucleophile. The name
nucleophile “nucleus-loving” and indicates that it attacks regions of low electron density
(positive centres) in the substrate molecule. Nucleophiles are electron-rich. They may be
negative ions (including carbanions) or neutral molecules with free electron pairs. Examples are
CI-, Br- , I-, CN-, OH-, NH3, RNH2, H2O, ROH.
Nucleophilic substitution reactions:
When a substitution reaction involves the attack by a nucleophile, the reaction is referred to as
SN(S stands for substitution and N for a nucleophile).
Organometallic compounds:
Organometallic compounds are compounds containing a carbon-metal bond. They are named as
Alkyl metals.
CH3CH2Li (CH3CH2)4Pb
Ethyl lithium Tetraethyl lead
Free radical bond formation:
It is not uncommon for an atom to complete its outer shell by sharing an electron with another
atom and forming a bond. Free radicals form when one of these weak bonds between electrons is
broken and an uneven number of electrons remain. This means the electron is unpaired, making
it chemically reactive.

66
 Chapter -Four

Pharmacology

Pharmacology: The word “Pharmacology” derive from the Greek words “Pharmacon” means
Drug, “logos’’ means knowledge.
Pharmacology embraces the knowledge of history, sources, physical, and chemical properties,
compounding, biological and physiological effects, mechanism of action, distribution of drugs,
biotransformation, excretion and therapeutic and other use of drugs.
Pharmacokinetics: The word pharmacokinetics is derived from two words, “Pharmacon”
meaning Drug and “kinetics” meaning movement.
It can be defined as the branch of pharmacology that deals with the absorption, distribution,
metabolism and elimination of drugs and their relationship with the onset, duration and intensity
of the drug effect. In other words, what the body does to the drug is called pharmacokinetics.
Pharmacodynamics: The word pharmacodynamics is derived two word, “Pharmacon’’ meaning
Drug and “dynamics” meaning power.
It can be defined as the branch of pharmacology that deals with the mechanism of action and the
relation between the drug concentration and its effect.
It is the study of physical and chemical effects of drugs on body, parasites and microorganism. In
other words, what the drug does to the body is called pharmacodynamics.
Therapeutics: The branch of pharmacology that deals with the art and science of treatment of
disease. It is the application of pharmacological information together with the knowledge of
disease, for the prevention and cure of the disease.
Pharmaceutics: It can be defined as the branch of pharmacology that deals with the preparation
and dispending of a drug dosage formulation suitable for administration.
Pharmacognosy: The branch of pharmacology that deals with source, identification,
purification, and isolation of drug.
Pharmacogenetics: The branch of pharmacology that examines the relation of genetic factors to
variations in response to drugs.
Chemotherapy: Chemotherapy refers to the treatment of disease by means of chemicals that
have a specific toxic effect upon the disease-producing microorganisms or that selectively
destroy cancerous tissue.
Toxicology: Toxicology is the branch of pharmacology which includes the study of adverse
effects that occur in living organisms due to chemicals. It deals with the observing and reporting

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symptoms, mechanisms, detection and treatments of toxic substances, in particular relation to the
poisoning of humans.
Posology: The branch of pharmacology and therapeutics concerned with a determination of the
dosages of drugs; the science of dosage.
Clinical pharmacology: Clinical pharmacology is the scientific study of drug in human or
animal. It deals with the pharmacokinetic and pharmacodynamics investigations in healthy or
diseased individuals.
Pharmacoeconomics: Pharmacoeconomics refers to the cost of drugs. In this discipline the cost
of one drug is compared with another for same use. The inexpensive drugs are preferred.
Pharmacogenomics: Pharmacogenomics is the study of how genes affect a person's response to
drugs.
It is the broader application of genomics technologies to new drug discovery and further
characterization of older drugs.
Pharmacoepidemiology: Pharmacoepidemiology is the study of the uses and effects of drugs in
well-defined populations. The effects may be good or harmful.

Pharmacopoeia

Pharmacopoeia: It is an approved book of drugs, their compositions, doses, side effects and
their constituents. It is very useful for pharmacists who work in hospital or in clinics. An
authoritative treatise on drugs and their preparations; a book containing a list of products used in
medicine, with descriptions, chemical tests for determining identity and purity and formulae of
certain drugs and preparations.
Name of different pharmacopoeia:
 British Pharmacopoeia (BP)
 United States Pharmacopoeia (USP)
 British National Formularies (BNF)
 National Formularies (NF)
 British Pharmacopoeia Codex (BPC)
 European Pharmacopoeia (EP)
 Indian Pharmacopoeia (IP)
 Japanese Pharmacopoeia (JP)
 World Health Organisation Pharmacopoeia (WHOP)
 Bangladesh National Formulary (BNF)
Note: There is no pharmacopoeia in Bangladesh, we usually follow the British pharmacopoeia
(BP).

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 Drug and Medicine

Drug: A drug is a substance that acts on the living body to alter the physiological process and
are used for prevention, diagnosis, control and treatment of disease.
Example: Paracetamol, Rabeprazole, Esomeprazole.
Sources of Drugs:
Plant sources Digitalis, Morphine, Atropine.

Animal sources Insulin, Heparin, Serum, Thyroxin,

Vitamin-A
Micro-organism sources Penicillin, Streptomycin, Chrysogenum.

Minerals sources MgSO4,7H2O, Ferrous Sulphate,

Liquid paraffin.
Synthetics sources Aspirin, Procaine, Sulfonamides.
Semi- synthetic sources Ampicillin, Tetracycline
Recombinant DNA technology Human insulin. Growth hormone.

Ideal properties of drugs:

 A drug must have appropriate size, electrical charge, shape, and atomic composition.
 It must have good efficacy and potency.
 It must have least adverse effects.

Groups of the drug

There are five groups of drugs:

1. Over the counter drugs (OTC): The drugs which are available without prescription are
called OTC drugs, they are highly safe producing least toxic effects. E.g. Antacid,
Paracetamol, Aspirin, Iron tablet, Vitamin tablet, Antiemetic drug.
2. Prescription drugs: The drugs which are available only on prescription are called
prescription drug. E.g. Anti-biotics, Vaccine, Antidepressant.
3. Controlled drugs: The drugs which can never be dispensed with prescription are called
controlled drugs. E, g. Narcotics, Hallucinogens (LSD, pethidine, heroine) etc. They produce
addiction.
4. Experimental drugs: The drugs which are on trial are called experimental drugs. Example-
Endrophonium in myasthenia gravis, BaSO4 etc.
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5. Official drug: The drugs which are included in pharmacopoeia.
Medicine: A medicine is any substance or substances used in treating disease or illness.
Difference between drugs and medicine:
Point Drug Medicine
Definition Substances which act Substances that have definite form and
on the body and are therapeutic use for treatment
used for prevention,
diagnosis and
treatment
Amount Drug doesn’t have Medicine has a definite form and dose
any definite form and
dose
Potency Drugs are the active Medicines are the administrative form of
potent compound drug
Compare All drugs are not All medicines are drugs
medicines
Example Paracetamol, Napa (paracetamol) 500 mg tablet,
Renitidine Neocoptin-R (Ranitidine) 150 mg tablet

Difference between food and drug:

Drug Food

A drug is any substance or product that is used Food is the active ingredient of the body
or intended to be used to modify or explore which provides energy and enhances the
physiological states for the benefit or the physiological process of the body.
recipient.
Drug has no caloric effect. Food has caloric effect.
Drug does not store energy. Food store energy.
Drug must be excreted from the body. Food can assimilate in the body.
E.g. Digoxin, tetracycline. E.g. Rice, meat, egg, etc.

Prodrug

Prodrug: The drugs which do not produce any pharmacological effect until they are chemically
altered within the body are called prodrug. Example- Levodopa, Castor oil.

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Example of prodrug:
Prodrug Active form
Aspirin Salicylic acid
Diazepam Oxazepam
Codein Morphine
Levodopa Dopamine
Prontosil Sulphonamide

Advantages of using prodrug:

 To avoid toxicity.
 To increase bio-availability.
 Avoiding first pass metabolism.
 Reducing local adverse effects of drug.
 To overcome pharmaceutical formulation.

Placebo

An inactive substance or other form of therapy administered to a patient usually to compare its
effects with those of a real drug or treatment but sometimes for the psychological benefit to the
patient through his believing he is receiving treatment.
The inactive substances are – Starch, Glucose, Sucrose, Lactose, Dextrose, etc.
Uses of placebo:
 To determine the effect of medicine.
 To control scientific evaluation of drug.
 To prevent habituation and addiction of drug.
 To satisfy the patient not by any pharmacological action but by psychological means.

Drug accumulation

When doses are given repeatedly, the drug will not be immediately eliminated from the body but
will accumulate in the body until dosing stop. This is called drug accumulation (i.e. drug
absorption is more than drug elimination).

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 Drug tolerance

Gradual diminution of tissue response to a drug due to repeated administration is called drug
tolerance.
Stage of tolerance:
Habituation Addiction Dependence Tolerance

Drug addiction

It is a state of periodic or chronic intoxication produced by the repeated consumption of certain

drugs.
Drug addiction may be physical or psychological or both.

Drug habituation

Condition resulting from repeated consumption of certain drugs, characterized by psychological

dependence. Example- Tobacco, caffeine, etc.

Drug dependence

On repeated administration of certain drugs, the individual may be both psychologically and
physiologically dependent on them. This phenomenon is called drug dependence.
Types of drug dependence:
1. Psychic or emotional
2. Physical dependence

Drug abuse

Self-administration of drug for non-therapeutic purpose, almost always for altering

consciousness is called drug abuse. Example- Chronic intoxication with alcohol.
Commonly abused drugs (centrally acting) are Narcotics, Marijuana, Barbiturates, Alcohol, Anti-
depressants etc.

Tachyphylaxis
Rapidly developed tolerance due to rapid administration of drug within a short interval of time is
called tachyphylaxis. It is less commonly seen than tolerance and also called acute tolerance.

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 Receptor

Receptor: A receptor is a protein macro-molecules structure and protein in nature present in the
cell membrane with which messenger combine reversibly or irreversibly in order to produce
biological effect.
Drug + Receptor = Drug- receptor complex
Classification of receptors:
According to both molecular structure and the nature of transduction mechanism:
Type-1: Ion channel (Ligand- gated ion channel):
Ligand-gated ion channels which are membrane bound receptors directly linked to an ion
channel. They are also known as ionotropic receptors.
Examples include the nicotine acetylcholine receptor, glutamate receptor and the GABA-A
receptor.

Figure: Ion channel (Ligand- gated ion channel).

Type-2: protein coupled receptor (G-protein coupled receptor):

G-protein coupled receptors are membrane bound receptors coupled to G-proteins. After
activation of the G-proteins a variety of biochemical signal transduction pathways can be
activated. Many chemicals messengers, like hormones and various neurotransmitters act through
G-protein coupled receptors. They are also known as metabotropic receptors or 7-trnasmembrane
receptors.

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 Examples include the muscarinic acetylcholine receptors, adrenergic receptors.

Figure: Protein coupled receptor (G-protein coupled receptor).

Type-3: Enzymatic receptor (Tyrosine – kinase linked receptors):
Tyrosine – kinase linked receptors which are membrane bound receptors and contain an intrinsic
enzymatic function (tyrosine kinase activity) in their intracellular domain, upon combination
with ligand like insulin, the receptor is activated and is able to phosphorylate tyrosine residues of
other intracellular proteins. Protein phosphorylation is one of the underlying mechanisms of the
regulation of protein function. Examples include the receptors for insulin and various cytokines
and growth factors.
Type-4: Intracellular receptors (Ligand- activated transcription factors):
Ligand- activated transcription factors, which are located in the cytosol, upon binding of the
appropriate chemical.
Example-Steroid hormones, the activated receptors translate to the nucleus and initiate gene
transcription. These are also known as nuclear receptors.
Examples include the receptors for steroid hormones, thyroid hormones and Vitamin-D.
According to location
According to location receptor are three types:
(a) Membrane receptor: The receptors of this group are situated on the external surface of the
plasma membrane of the target cell. Example- alpha and beta adrenoceptors, cholinergic
receptors and all peptide hormone receptors.

(b) Cytoplasmic receptor: The receptors of this group are situated in the cytoplasm of target
cells and combine with the drugs that mimic or block the actions of steroids hormones.
Example- steroid hormone receptors.
(c) Nuclear receptor: The receptors of this group are situated in the nucleus of the target cells.
Example- thyroid hormone receptors, sex hormones receptors etc.

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According to function:
1. Active receptor: About 1-2% of the receptors in the body are active receptors. They situated
on the cell membrane.
(a) Histamine receptor: H1 receptor, H2 receptor.
(b) Cholinergic receptor: Muscarinic receptor, Nicotinic receptor.
(c) Adrenergic receptor: Alpha receptor, Beta receptor.

2. Silent receptor: A silent receptor is that to which the agonist may become attached but
which is incapable of producing a pharmacological response. E.g. Plasma protein.

3. Spare receptor: About 98-99% of receptors are spare, usually they are inactive but when
active receptors are saturated, they become active. E.g. Nicotinic receptor.

Agonist, Antagonist, Partial agonist, Drug antagonism

Agonist: An agonist is a substance that binds to a receptor of a cell and activates the receptor to
produce a biological response by it cell. Example- Acetyl choline, Nicotine, Nor-adrenaline ect.
Antagonist: A substance that does not activate the receptor are termed antagonist (antagonist
occupy the receptor without activating them, therefore agonist cannot act on receptor). E.g.
Propranolol. Ranitidine, Naloxone.
Partial agonists: Partial agonists are drugs that bind to and activate a given receptor, but have
only partial efficacy at the receptor relative to a full agonist. Example- Pindolol.
Drug antagonism: Drug antagonism means abolition or inhibition of the effect of one drug by
another, so that the combined action of the two drugs is less than that of individual one.

Routes of drug administration

The route of administration is determined by the properties of the drug (for example, water or
lipid solubility, ionization) and by the therapeutic objectives (for example, the desirability of a
rapid onset, the need for long-term treatment, or restriction of delivery to a local site). Major
routes of drug administration include enteral, parenteral and topical among others.
The main routes of drug administration are:
(A) Systemic route:
(1) Enteral or alimentary routes: Enteral administration is the safest and most common,
convenient and economical method of drug administration.
(a) Oral: Oral administration provides many advantages. Oral drugs are easily self-
administered, and toxicities and/or overdose of oral drugs may be overcome with antidotes,
such as activated charcoal.

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(b) Sublingual/buccal: Placement under the tongue allows a drug to diffuse into the capillary
network and enter the systemic circulation directly.

(c) Rectal:50% of the drainage of the rectal region bypasses the portal circulation, the
biotransformation of drugs by the liver is minimized with rectal administration. The rectal
route has the additional advantage of preventing destruction of the drug in the GI
environment. This route is also useful if the drug induces vomiting when given orally, if the
patient is already vomiting or if the patient is unconscious.

Figure: Commonly used routes of drug administration. IV = intravenous; IM =

intramuscular; SC = subcutaneous

(2) Parenteral routes: Parenteral administration is used for drugs that are poorly absorbed from
the gastrointestinal (GI) tract (for example heparin) or unstable in the GI tract (for example,
insulin). Parenteral administration is also used if a patient is unable to take oral medications
(unconscious patients) and under circumstances that require a rapid onset of action.
The three major parenteral routes:
(a) Intravenous (IV): IV injection is the most common parenteral route. It is useful for drugs
that are not absorbed orally, such as the neuromuscular blocker rocuronium.

(b) Intramuscular (IM): Drugs administered IM can be in aqueous solutions, which are
absorbed rapidly, or in specialized depot preparations, which are absorbed slowly. Depot
preparations often consist of a suspension of the drug in a nonaqueous vehicle such as
polyethylene glycol.

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(c) Subcutaneous (SC): This route of administration, like IM injection, SC injection provides
absorption via simple diffusion and is slower than the IV route. SC injection minimizes the
risks associated with IV injection.

(B) Local routes:

(a) Inhalation: Inhalation routes provide rapid delivery of a drug across the large surface area
of the mucous membranes of the respiratory tract and pulmonary epithelium.

(b) Nasal inhalation: This route involves administration of drugs directly into the nose.
Examples of agents include nasal decongestants such as oxymetazoline and corticosteroids,
such as mometasone furoate.

(c) Intrathecal/intraventricular: The blood–brain barrier typically delays or prevents the

absorption of drugs into the central nervous system (CNS). When local, rapid effects are
needed, it is necessary to introduce drugs directly into the cerebrospinal fluid. For example
intrathecal amphotericin B is used in treating cryptococcal meningitis.

(d) Topical: Topical application is used when a local effect of the drug is desired. For example,
clotrimazole is a cream applied directly to the skin for the treatment of fungal infections.

(e) Transdermal: This route of administration achieves systemic effects by application of drugs
to the skin, usually via a transdermal patch. The rate of absorption can vary markedly,
depending on the physical characteristics of the skin at the site of application, as well as the
lipid solubility of the drug.

Drug dose

It is the amount of the drug, which is required to produce certain measurable biological response,
either at once after sometime of administration.
The dose is taken at a time or in fractional amount within particular time to get biological
response.
Dosage:
Determination of the amount, frequency and number of doses of drug for a patient is called
dosage.
Types of dose
Therapeutic (effective) dose: Dose that is required to produce the optimal therapeutic effect is
called therapeutic (effective) dose.

ED50: Median effective dose: The dose required to achieve 50%of the desired response in 50%
of the population is called ED50.

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 TD50: Median Toxic dose: The dose required to get 50% of the population reporting this
specific toxic effect is called TD50.

LD50: Median lethal dose: The dose required to achieve 50% mortality from toxicity is called
LD50.

EC50: Half maximum effective concentration: The concentration of a drug at which 50% of
its maximum response is observed is called EC50.

LC50: Half lethal concentration: The concentration of a drug at which 50% mortality from
toxicity is observed is called LC50.

Toxic dose: The amount of a substance that may be expected to produce a toxicity.

Maximum dose: The largest dose of a medicine or drug consistent with safety and produce no
toxic effect is called maximum dose.

Lethal dose: Amount of dose that causes death of certain (%) of experimental animals. (It may
or may not be 100%).
Fatal dose: Amount of dose that causes death of 100% of experimental animals (or when lethal
dose reaches 100%, LD100).
Booster dose: Dose that is given after sometime (months or years) of an initial dose to enhance
the effect. E.g. Anti-tetanus, Anti-poliomyelitis booster dose is given after 5 years of initial
dose.
Test dose: Amount of drug given some initially (before giving full therapeutic dose) to see the
response of tissue to the drug is called test dose.
Ceiling dose: Dose by which the ceiling effect is obtained is called ceiling dose.
Ceiling effect: The degree of effect produced by increasing doses of a drug eventually reaches a
steady level. This phenomenon is called ceiling effect.
Loading dose: The loading dose is one or a series of doses that may be given at the onset
therapy with the aim of achieving the target concentration rapidly.
Maintenance dose: The dose required to maintain the desired effect that is achieved by previous
dose.
Adult dose: According to British pharmacopoeia, the dose given in between 20 to 60 years of
age is known as adult dose.
Pediatric dose: The dose of medicament to be administered to a child or infant.

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 Therapeutic index

Therapeutic index is the ratio between the median lethal dose and the median effective dose.

So, therapeutic index = LD50/ED50 (in animal studies or for humans).

Or, Therapeutic index is the ratio between the median toxic dose and the median effective dose.
So, therapeutic index = TD50 /ED50 (in clinical medicine).
Significance of therapeutic index:
It provides crude measure of the safety of any drug as used in practice. An ideal drug,
therapeutic index = LD99/ED1.
 More therapeutic index: more safety and vice versa (highly selective drug). For example-

(a) Chemotherapeutic drugs:

LD50 = 16. So, the chemotherapeutic drugs are safer than the
ED50 = 4. anticancer drugs.

T.I = 4.
(b) Anti-cancer drugs:
Term Meaning
LD50 = 16.
'ED' Effective Dose
ED50= 8. 'TD' Toxic Dose
T.I = 2. 'LD' Lethal Dose
 Less T.I: less safety. Non-selective drug. 'TI' Therapeutic
 For safer therapeutic application of a drug T.I must be more Index
than one. 'TR' Therapeutic Ratio
 A drug may have different therapeutic index depending on its
therapeutic application.
For example: Aspirin in headache: ED50 is low. Aspirin in rheumatic fever: ED50 is greater than
ED50 for headache.
 For evaluation of new drugs T.I has great significance.
Limitation of therapeutic index:
a. It is based on animal toxicity data, which may not reflect forms of toxicity that are important
clinically.
b. It takes no account of idiosyncratic toxic reaction.

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Standard margin of safety:
Therapeutic index may be misled if log dose response curves for effectiveness and toxicity have
different slopes rather than parallel. So, standard margin of safety may be useful-
It can be expressed as follows: LD1
Standard margin of safety= − 1 × 100
ED99
(It shows the % by which ED50 must be increased in order to cause toxic effect in 1% of
population.

Effects of drugs

A. Therapeutic effects.
B. Adverse effects.
C. Side effects.
D. Untoward/Unwanted effect.
(a) Qualitative:( example- Idiosyncrasy, Hypersensitivity)
(b) Quantitative (example-Drug intolerance)
E. Toxic effects.
F. Teratogenic effect.

Therapeutic effects

Therapeutic effects: It is desired or beneficial effect. It refers to the responses after a treatment
of any kind the results of which judged to be desirable and beneficial.

Adverse effects

Adverse effect: A harmful or abnormal result. An adverse effect may be caused by

administration of a medication or by exposure to a chemical and be indicated by an untoward
result such as by illness or death.

Side effects
Side effects: Therapeutically undesired and unavoidable effects that occur in association with
beneficial effect at the normal therapeutic dose of a drug is called side effect.

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 Untoward/Unwanted effects

Untoward/Unwanted effects: Harmful or seriously unpleasant effects occurring at doses

intended for therapeutic effect and which call for reduction of dose or withdrawal of the drug
and/or forecast hazards from future administration.

Toxic effects
Toxic effects: Undesired effect produced by normal dose for prolong use or high dose for
normal period. Example- Chloramphenicol causes aplastic anaemia.
Types of toxic effect:
1. Acute toxic effect: Immediate production of toxic effect after drug administration is called
acute toxic effect.
2. Chronic toxic effect: Toxicity developing gradually due to prolong use of drugs is called
chronic toxic effect.

Hypersensitivity reaction

Allergic reactions to drugs are the resultant of the interaction of drugs or metabolites with patient
and disease and subsequent re-exposure.
It may be due to: (a) Antigen- antibody reaction. (b) Cell mediated immune reaction.

Idiosyncrasy

Unusual drug response that occurs in a small minority of individuals within therapeutic dose is
called idiosyncrasy.
Or, inherited abnormal response to drugs mediated by single gene is called idiosyncrasy and
cause increased, decreased and bizarre response to drugs.
 It is a qualitative abnormal, harmful effect of drug.
 Reaction may occur with low doses.
 Genetic factor may be responsible.

Teratogenic effect

Harmful effect on the fetus within the uterus resulting in a gross malformed child is called
teratogenic effect and the drug is called teratogenic drug.
In the human fetal development passes through 3 phases
1. Blastocyst formation (cell division occur).

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2. Organogenesis (first trimester of pregnancy).
3. Histogenesis and maturation of function.
Difference between side effect and toxic effect:
Side effect Toxic effect
It is normal pharmacological effect of drug. It is noxious effect of a drug.

Occurs at normal therapeutic dose. Occurs due to overdose or repeated dose.

Does not indicate reduction or cessation of Indicate reduction or cessation of therapy.
therapy.
No need of treatment. Requires treatment.

It is unavoidable. It can be avoided by careful and wise use of

drug.

Difference between potency and efficacy:

Potency Efficacy
Comparative measure of different doses of Ability of drug after binding with receptor to
two drugs that are needed to produce the same initiate change which leads to effects is called
effect is called potency. efficacy.
It is the amount of drug in relation to its It is the capacity of a drug to produce an
effect. effect and refers to maximum such effect.
Potency does not help to choose among drugs. Efficacy helps to choose among drugs.
It is absolute potency. It is therapeutic potency.
Potency determines the administered dose of Efficacy determines clinical effectiveness of a
the chosen drug. drug.
Potency ≡ Affinity. Efficacy ≡ Intrinsic activity.

Affinity: Tendency of drug to bind with receptor is termed as affinity.

Affinity≡Potency

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 Analgesics

The term analgesics encompasses a class of drugs that are designed to relieve pain without
causing the loss of consciousness are called analgesics. The pain may be somatic or visceral.
Somatic pain: Headache, pain in muscles and joints, etc.
Visceral pain: Spasmodic pain in any viscera such as kidney, urinary bladder, stomach, liver,
spleen, etc.
Types of analgesics:
1. Narcotic analgesics: Drugs which reduce pain from the viscera and produce narcosis
(depression of CNS) and addiction. Example- Morphine, Hydromorphone, Fentanyl,
Levorphanol, Naloxone, Tramadol, etc.

2. Non-narcotic analgesics: Drug that relief pain arising from musculoskeletal system without
producing narcosis and addiction. Example-Ibuprofen, Naproxen, Ketoprofen.

Non-narcotic analgesics

Nonsteroidal anti-inflammatory drugs (NSAIDs): Nonsteroidal anti-inflammatory drugs

(usually abbreviated to NSAIDs , also called nonsteroidal anti-inflammatory agents/analgesics
(NSAIAs) or nonsteroidal anti-inflammatory medicines (NSAIMs) are a drug class that groups
together drugs that provide analgesic (pain-killing) and antipyretic (fever-reducing) effects and,
in higher doses, anti-inflammatory effects.
Medical uses: Nonsteroidal anti-inflammatory drugs are usually indicated for the treatment of
acute or chronic conditions where pain and inflammation are present. Research continues into
their potential for prevention of colorectal cancer and treatment of other condition, such as
cancer and cardiovascular disease.
NSAIDs are generally indicated for the symptomatic relief of the following condition:
 Pyrexia
 Osteoarthritis
 Acute gout
 Menstrual pain
 Metastatic bone pain
 Headache and migraine
 Postoperative pain
 Mild to moderate pain due to inflammation and tissue injury
 Muscle stiffness and pain due to Parkinson’s disease

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Mechanism of action of NSAIDs:
NSAIDs act by inhibiting the synthesis of prostaglandins enzyme cyclo-oxygenase which is
necessary for the synthesis of prostaglandins (PG). Inhibition of the fastidious enzyme can occur
by following mechanism:
 An irreversible inactivation (aspirin, indomethacin).
 A rapid reversible competitive inhibition (ibuprofen).
 A rapid reversible non-competitive inhibition (paracetamol).

Membrane phospholipids

Phospholipase A2

Arachidonic acid

(-) NSAIDs

Cyclo-oxygenase (COX)

COX-1 COX-2
“Constitutive” “Inducible”

Prostaglandin (PG) prostaglandin (PG)

PGA1 PGG2
PGE1 PGH2 PGE2
PGE2 PGF2∝

Protection of Hemostasis Mediation of pain,

gastric mucosa inflammation and
fever
Adverse effects of NSAIDs:
Common adverse effects of NSAIDs:
GIT: Gastric ulceration, Dyspepsia, Nausea, Vomiting, Erosion.
Hypersensitivity: Rash, Asthma.
Liver: Liver damage

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Kidney: Renal tubular necrosis, Acute renal failure.
Blood: Impaired clotting.

Anti-inflammatory drugs

SELECTIVE COX-2 INHIBITORS

NSAIDs

Aspirin, Diclofenac Celecoxib

Etodolac, Diflunisal Lumiracoxib
Fenoprofen, Flurbiprofen Valdecoxib (Withdrawn from market)
Ibuprofen, Indomethacin Rofecoxib (Withdrawn from market)
Meclofenamate
Ketorolac, Ketoprofen
Mefenamic acid
Meloxicam, Naproxen etc.

OTHER ANALGESICS

Acetaminophen

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 Gastrointestinal system

Peptic ulcer disease:

 Infection with gram-negative Helicobacter pylori
 The use of nonsteroidal anti-inflammatory drugs (NSAIDs)
 Increased hydrochloric acid secretion
 Inadequate mucosal defense against gastric acid
Treatment approaches:
1. Eradicating H.pylori infection.
2. Reducing secretion of gastric acid or neutralizing the acid with the use of PPIs or H2-
receptor antagonists.
3. Providing agents that protect the gastric mucosa from damage such as misoprostol and
sucralfate.

DRUGS USED TO TREAT PEPTIC ULCER DISEASE

INHIBITORS OF PROTON PUMP H2- HISTAMINE RECEPTOR BLOCKERS

Lansoprazole Cimetidine
Omeprazole Famotidine
Pantoprazole Nizatidine
Esomeprazole Ranitidine
Rabeprazole

ANTIMICROBIAL AGENTS ANTACIDS

Amoxicillin Aluminum hydroxide

Bismuth compound Sodium citrate
Clarithromycin Calcium carbonate
Metronidazole Magnesium trisilicate
Tetracycline Magnesium hydroxide
Sodium bicarbonate

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 ANTIMUSCARINIC AGENTS MUCOSAL PROTECTIVE AGENTS

Pirenzepine
Dicyclomine Bismuth subsalicylate
Mepenzolate Sucralfate
Hyoscyamine

PROSTAGLANDINS

Misoprostol

Classification of antacids:
(1) Systemic antacids (2) Non-systemic antacids
NaHCO3, NaCO3, Magnesium trisilicate, Al(OH)3,
KHCO3, Na-citrate Ca(OH)2, Mg(OH)2, MgCO3.
Na-acetate.

Regulation of gastric acid secretion:

Gastric acid secretion by parietal cells of the gastric mucosa is controlled by acetylcholine,
histamine, prostaglandins E2 and I2, and gastrin. The receptor-mediated binding of acetylcholine,
histamine, or gastrin results in the activation of a proton pump (H+/K+- ATPase) that secretes
hydrochloric acid (HCI) into the lumen of the stomach. In contrast, receptor binding of
prostaglandins E2 and I2 diminishes gastric acid production.
Histamine binding causes activation of adenylyl cyclase, whereas binding of prostaglandin E2
and I2 inhibits this enzyme. Gastrin and acetylcholine act by inducing an increase in intracellular
calcium levels.

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H2-receptor antagonists:
Mechanism of Actions: The histamine H2-receptor antagonists - cimetidine, ranitidine,
famotidine, and nizatidine - act on H2-receptors in the stomach, blood vessels, and other sites.
They are competitive antagonists of histamine and are fully reversible. By competitively
blocking the binding of histamine to H2 receptors, these agents reduce intracellular
concentrations of cyclic AMP and thereby, secretion of gastric acid.
These agents completely inhibit gastric acid secretion induced by histamine, gastrin. However,
they only partially inhibit gastric acid secretion induced by acetylcholine or bethanechol.

Therapeutic uses:
Peptic ulcers, Zollinger-Ellison syndrome (hypersecretory condition), acute stress ulcers,
Gastroesophageal reflux disease (heartburn)
Adverse reaction:
Diarrhea, headache, drowsiness, fatigue, muscular pain, constipation, confusion, delirium,
hallucinations, slurred speech, headaches, galactorrhea in women and gynecomastia, reduced
spermcount, thrombocytopenia and impotence in men.

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 Inhibitors of the H+/K+-ATPase proton pump

Mechanism of action:
The first proton pump inhibitor was the substituted benzimidazole omeprazole, which
irreversibly inhibits the H+/K+ ATPase (the proton pump), suppressing secretion of hydrogen
ions into the gastric lumen, the terminal step in the acid secretory pathway. Both basal and
stimulated gastric acid secretion is reduced. The drug is a weak base and accumulates in the acid
environment of the canaliculi of the stimulated parietal cell where it is activated. This
preferential accumulation means that it has a specific effect on these cells. Other proton pump
inhibitors include esomeprazole, lansoprazole, pantoprazole and rabeprazole.
At standard doses, both omeprazole and lansoprazole inhibit basal and stimulated gastric acid
secretion more than 90%. Acid suppression begins within 1 to 2 hour after the first dose of
lansoprazole, and slightly earlier with omeprazole.
Therapeutic uses:
It is used in short-term treatment of erosive esophagitis and active duodenal ulcer, and for long-
term treatment of pathologic hypersecretory conditions (for example, Zollinger-Ellison
syndrome), gastroesophageal reflux disease. It is successfully used with antimicrobial regimens
to eradicate H.pylori.
Adverse Effects:
Headache, diarrhoea (both sometimes severe), and rashes, dizziness, somnolence, mental
confusion, impotence, gynaecomastia, pain in muscles and joints and liver disease

Antacids

Antacids: Antacids are weak bases that react with gastric acid to form water and a salt, thereby
diminishing gastric acidity. Since pepsin is inactive at pH>4.0, antacids also reduce peptic
activity. They may have other actions as well, such as reduction of H. pylori colonization and
stimulation of prostaglandin synthesis.
Different types of antacids:
Most antacids in common use are salts of magnesium and aluminium. Magnesium salts cause
diarrhoea and aluminium salts constipation, so mixtures of these two can happily be used to
preserve normal bowel function.
Some preparations of these substances (e.g. magnesium trisilicate mixture and some proprietary
aluminium preparations) contain high concentrations of sodium and should not be given to
patients on a sodium-restricted diet.

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Magnesium hydroxide: Magnesium hydroxide is an insoluble powder that forms magnesium
chloride in the stomach. It does not produce systemic alkalosis, because Mg2+ is poorly absorbed
from the gut.
Another salt, magnesium trisilicate is an insoluble powder that reacts slowly with the gastric
juice, forming magnesium chloride and colloidal silica. This agent has a prolonged antacid effect
and it also adsorbs pepsin.
Aluminium hydroxide gel: Aluminium hydroxide gel forms aluminium chloride in the stomach,
when this reaches the intestine, the chloride is released and is reabsorbed.
Aluminium hydroxide raises the pH of the gastric juice to about 4 and also adsorbs pepsin. Its
action is gradual and its effect continues for several hours.
Colloidal aluminium hydroxide combines with phosphates in the gastrointestinal tract and the
increased excretion of phosphate in the faeces that occurs results in decreased excretion of
phosphate via the kidney. This effect has been used in treating patients with chronic renal failure.
Sodium bicarbonate: Sodium bicarbonate acts rapidly and is said to raise the pH of gastric juice
to about 7.4. Carbon dioxide is liberated and this causes eructation (belching). The carbon
dioxide stimulates gastrin secretion and can result in a secondary rise in acid secretion. Because
some sodium bicarbonate is absorbed in the intestine, large doses or frequent administration of
this antacid can cause alkalosis, the onset of which can be insidious. To avoid this possibility,
sodium bicarbonate should not be prescribed for long-term treatment nor should it be given to
patients who are on a sodium-restricted diet.
Therapeutic uses:
Aluminum- and magnesium-containing antacids can promote healing of duodenal ulcers.
Adverse effects:
Aluminum hydroxide may be constipating, Magnesium hydroxide may produce diarrhea.
Preparations that combine these agents aid in normalizing bowel function. In addition to the
potential for systemic alkalosis, NaHCO3 liberates CO2, causing belching and flatulence.
Absorption of cations from antacids (Mg2+, AI3+, Ca2+) is usually not a problem in patients with
normal renal function, but the sodium content of antacids can be an important consideration in
patients with hypertension or congestive heart failure.
Antimuscarinic agents:
Muscarinic receptor stimulation increases gastrointestinal motility and secretory activity.
Cholinergic antagonists such as hyoscyamine, are used as adjuncts in the management of peptic
ulcer disease and Zollinger-Ellison syndrome, particularly in patient’s refractory to standard
therapies.
In contrast to the classic anticholinergics, the relatively specific muscarinic M1-receptor
antagonist pirenzepine is under investigation for its clinical usefulness as an antisecretory agent.

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Pirenzepine suppresses basal and stimulated gastric acid secretion at doses having a minimal
effect on salivary glands, the heart and eye.
Prostaglandins:
Prostaglandins E2 and I2, produced by the gastric mucosa, inhibit secretion of HCI and stimulate
secretion of mucus and bicarbonate (cytoprotective effect). A deficiency of prostaglandins is
thought to be involved in the pathogenesis of peptic ulcers.
Misoprostol, a stable analog of prostaglandin E1, is currently the only agent approved for
prevention of gastric ulcers induced by non- steroidal anti-inflammatory agents (NSAIDs). It is
less effective than H2 antagonists for acute treatment of peptic ulcers. Although misoprostol has
cytoprotective actions, it is clinically effective only at higher doses that diminish gastric acid
secretion. Like other prostaglandins, misoprostol produces uterine contractions and is
contraindicated during pregnancy. Dose-related diarrhea and nausea are the most common
adverse effects.
Mucosal Protective Agents:
These compounds, known as cytoprotective, have several actions that enhance mucosal
protection mechanisms, thereby preventing mucosal injury, reducing inflammation, and healing
existing ulcers.
Sucralfate: This complex of aluminum hydroxide and sulfated sucrose, binds to positively
charged groups in proteins, glycoproteins etc. of both normal and necrotic mucosa. By forming
complex gels with epithelial cells, sucralfate creates a physical barrier that protects the ulcer
from pepsin and acid, allowing the ulcer to heal.
Although sucralfate is effective for the treatment of duodenal ulcers and prevention of stress
ulcers, its use is limited due to the need for multiple daily dosing and drug–drug interactions.
Because it requires an acidic pH for activation, sucralfate should not be administered with H2
antagonists or antacids. Little of the drug is absorbed systemically. It is very well tolerated.
Colloidal bismuth: Preparations of this compound effectively heal peptic ulcers. In addition to
their antimicrobial actions, they inhibit the activity of pepsin, increase mucus secretion and
interact with proteins in necrotic mucosal tissue to coat and protect the ulcer crater.
Difference between H2 blocker and PPI:
H2 blocker PPI
Block H2 receptors of the gastric parietal cells Inhibit proton pump by inhibiting H+, K+,
and inhibit HCL secretion. ATPase.
Inhibit both basal and food stimulated acid Inhibit both basal and food stimulated acid
secretion about 97%. secretion about 100%.
In effective in H2 antagonist resistance Effective in H2 antagonist resistance patients.
patients.

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Relatively short duration of action. Have a long -lasting effect on acid secretion.
Acidic environment is not required for Activation at acidic pH
activation.

Cardiovascular disease

Cardiovascular disease (also called heart disease) is a class of diseases that involve the heart, the
blood vessels (arteries, capillaries and veins) or both. Cardiovascular disease refers to any
disease that affects the cardiovascular system, principally cardiac disease, vascular disease of the
brain and kidney, and peripheral arterial disease. The causes of cardiovascular disease are divers
but atherosclerosis and /or hypotension are the most common.
Types of cardiovascular diseases:
 Aneurysm
 Angina
 Atherosclerosis
 Cerebrovascular accident (stroke)
 Cerebrovascular disease
 Congestive heart failure
 Coronary artery disease
Risk factors:
A risk factor is something that increases your likelihood of getting a disease. There are
several risk factors for CVD including:
 Smoking
 High blood pressure
 High blood cholesterol
 Being physically inactive
 Being overweight or obese
 Diabetes
 Family history of heart disease
 Ethnic background
 Sex- men are more likely to develop CVD at an earlier age than women
 Age- the older you are, the more likely you are to develop CVD
 Mental stress
 Alcohol

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 Common symptoms of cardiovascular disease

Symptoms of heart attacks:

Often there are no symptoms of the underlying disease of the blood vessels. A heart attack or
stroke may be the first warning of underlying disease. Symptoms of a heart attack include:
 Pain or discomfort in the center of the chest.
 Pain or discomfort in the arms, the left shoulder, elbows, jaw, back.
 The person may experience difficulty in breathing or shortness of breath; feeling sick or
vomiting, feeling light-headed or faint; braking into a cold sweat and becoming pale.
 Women are more likely to have shortness of breath, nausea, vomiting, and back or jaw
pain.
Symptoms of strokes:
The most common symptom of a stroke is sudden weakness of the face, arm, leg, most often
on one side of the body. Other symptoms include sudden onset of:
 Numbness of the face, arm, or leg, especially on one side of the body.
 Confusion, difficulty in speaking or understanding speech.
 Difficulty in seeing with one or both eyes.
 Difficulty in walking, dizziness, loss of balance or coordination.
 Severe headache with the no known cause; and
 Fainting or unconsciousness.

Aneurysm

An aneurysm is a localized, bloods-filled dilation of a blood vessel caused by disease or

weakening of the blood vessel. Aneurysm most commonly occur in arteries at the base of the
brain and in the aorta (the main artery coming out of the heart, a so- called aortic aneurysm).
Risk factor: Risk factors for an aneurysm are diabetes, obesity, hypertension, tobacco use and
alcoholism.

Angina pectoris

Angina pectoris is severe chest pain due to ischemia (a lack of blood and hence oxygen supply)
of the heart muscle, generally due to obstruction or spasm of the coronary arteries (the heart’s
blood vessels).
Risk factors: Cigarette smoking, diabetes, high cholesterol, high blood pressure, sedentary
lifestyle, family history of premature heart disease.

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 Atherosclerosis

Atherosclerosis is a disease affecting arterial blood vessels. It is a chronic inflammatory response

in the walls of arteries, in large part due to the accumulation of macrophage white blood cells
and promoted by low density lipoproteins (plasma proteins that carry cholesterol and
triglycerides) without adequate removal of fats and cholesterol from the macrophages by
functional high density lipoproteins (HDL). It is commonly referred to as a hardening of the
arteries. It is caused by the formation of multiple plaques within the arteries.
Risk factors: Diabetes, dyslipoproteinemia, high serum concentration of low density lipoprotein,
low serum concentration of functioning high density lipoprotein, tobacco smoking, high bold
pressure, advanced age, male sex, genetic abnormalities e, g. familial hypercholesterolemia.

Stroke

A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood
vessels supplying blood to the brain. This can be due to ischemia (lack of blood supply) caused
by thrombosis or embolism or due to a hemorrhage. As a result, the affected area of the brain is
unable to function, leading to inability to move one or more limbs on one side of the body,
inability to understand or formulate speech or inability to see one side of the visual field.
Strokes can be classified into two major categories: 1. Ischemic stroke 2. Hemorrhagic stroke
Risk factors: Advance age, hypertension, previous stroke or transient ischemic attack (TIA),
diabetes, high cholesterol, cigarette smoking and atrial fibrillation.

Congestive heart failure

(CHF)
Congestive heart failure (CHF) is a condition that can result from any structural or functional
cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of
blood throughout the body. It should not be confused with cardiac arrest.

Heart attack

Acute myocardial infarction is commonly known as heart attack. A heart attack occurs when the
supply of blood and oxygen to an area of heart muscle is blocked, usually by a clot in a coronary
artery.

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 CARDIOTONIC DRUGS

CARDIOTONIC GLYCOSIDES

SYMPATHOMIMETIC DRUGS

Digoxin Adrenaline
Digitoxin Dopamine
Isoprenaline

ANTI-CHOLINERGIC DRUGS
XANTHINE

Atropine Theophylline
Scopolamine Theobromide

IMIDAZOLE RING CONTAINING

DRUGS

Pilocarpine, Tolazoline, Phentomine

Anti-hypertensive drugs

Hypertension: Persistent rise of blood pressure above the upper limit of normal level according
to the age and sex of the individuals is called hypertension.
Normal limit of blood pressure
Systolic: 100 – 140 mm Hg (120 ± 20).
Diastolic: 60 – 90 mm Hg (75 ± 15).
Antihypertensive drug: Antihypertensive are a class of drugs that are used to treat
hypertension. Antihypertensive therapy seeks to prevent the complications of high blood
pressure such as stroke and myocardial infarction.
Classification of Antihypertensive drug:
A) Diuretics
1) Loop diuretics:

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  Furosemide , Torsemide.
2. Thiazide diuretics:
 Hydrochlorothiazide and Chlorothiazide.
3. Potassium-sparing diuretics:
 Amiloride , Triamterene.
B) Calcium channel blockers:
 Amlodipine, Felodipine, Cilnidipine, Isradipine, Nifedipine

C) Angiotensin-converting enzyme (ACE) inhibitors:

 Captopril, Enalapril, Fosinopril, Lisinopril, Ramipril.
Angiotensin II receptor antagonists:
 Fimasartan, Valsartan, Losartan, Telmisartan.
D) Sympatholytic (sympathoplegic) agents:
1. Centrally acting:
 Methyl-dopa, Clonidine.
2. Beta- adrenoceptor antagonists:
 Atenolol, Metoprolol, Nadolol, Nebivolol, Oxprenolol, Timolol, Pindolol.
3. Alpha- adrenoceptor antagonists:
 Doxazosin, Phentolamine, Indoramin, Phenoxybenzamine, Prazosin,
Terazosin, Tolazoline.
4. Mixed Alpha + Beta blockers:
 Bucindolol, Carvedilol, Labetalol.
5. Adrenergic neuron blockers:
 Guanethidine, Reserpine, ∝ −methyldopa.
E) Direct Vasodilators:
 Diazoxide, Hydralazine, Minoxidil, Prazosin, Nitroprusside.

Antidepressant drugs

Depression is characterized by altered mood. There is loss of interest in all usually pleasurable
outlets such as food, sex, work, friends, hobbies or entertainment. Diagnostic criteria include
 Depressed mood
 Diminished interest or pleasure in most or all activities
 Poor appetite or significant weight loss or increased weight gain
 Insomnia or hypersomnia
 Psychomotor agitation or retardation
 Feeling of hopelessness
 Loss of energy or fatigue
 Feeling of worthlessness, self-reproach or excessive or inappropriate guilt
 Complaints of or evidence of diminished ability to think or concentrate

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  Recurrent thoughts of death, suicidal ideation, wish to be dead or attempted
suicide
In depressive state there is a decrease in brain amine (nor-adrenaline, dopamine, 5-HT) concentration.

Antidepressants: Drugs that are used in the treatment of pathological depression are called
antidepressant.
All antidepressant drugs elevate the brain amine concentration in different ways.
Classification of Antidepressant drugs:
1. Tricyclic anti-depressants (TGA):
(First generation anti-depressants)
 Imipramine, Desipramine, Clomipramine, Amitriptyline, Nortriptyline, Protriptyline.

2. Atypical antidepressants:
(Second generation antidepressants)
 Amoxapine, Nomifensine, Mianserine, Maprotiline.

3. Monoamine oxidase inhibitors (MAO- I):

 Iproniazid, Phenelzine, Nialamide, Pargyline.

4. Selective serotonin reuptake inhibitors (SSRI):

 Fluoxetine, Paroxetine, Sertraline.

Tricyclic antidepressants

Amitriptyline is widely used antidepressant because it is most effective and less toxic than
MAO-inhibitors.
Tricyclic anti-depressants (TCA) are so called because their structure contain three benzene
rings.
Mechanism of action:
 TCAs inhibit the neuronal reuptake of norepinephrine and serotonin into presynaptic
nerve terminals. The TCAs lead to increased concentrations of monoamines in the
synaptic cleft, resulting in antidepressant effects.
 The TCAs also block serotonergic, α-adrenergic, histamine and muscurinic receptors.
Adverse effects:
Antimuscarinic effects: Blockade of acetylcholine receptors leads to-
 Blurred vision, Xerostomia (dry mouth), Urinary retention, Constipation, Aggravation of
glaucoma, Epilepsy.

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CNS effects:
 Sedation, Tremor, Agitation, Confusion, Parkinsonism.
CVS effects:
 Tachycardia, Hypertension, Arrhythmia.

Monoamine Oxidase Inhibitors

 Monoamine oxidase (MAO) is a mitochondrial enzyme found in neural and other tissues,
such as the gut and liver.
 In the neuron, MAO functions as a “safety value” to oxidatively deaminate and inactivates
any excess neurotransmitter molecules (norepinephrine, dopamine and serotonin).
 The MAO inhibitors may irreversibly or reversibly inactivate the enzyme, permitting
neurotransmitter molecules to escape degradation and therefore to both accumulate within
the presynaptic neuron and to leak into the synaptic space.
 The causes activation of norepinephrine and serotonin receptors and may be responsible for
the antidepressant action of these drugs.
 Three MAO inhibitors are currently available in the treatment of depression:
Phenelzine, Isocarboxazide, Tranylcypromine.
Therapeutic uses:
 MAO inhibitors are indicated for depressed patients who are unresponsive or allergic to
tricyclic antidepressants or who experience strong anxiety.
 Patients with low psychomotor activity may benefit from the stimulant properties of
MAO inhibitors.
 These drugs are also useful in the treatment of phobic states.
Adverse effects:
 Headache
 Tachycardia
 Nausea
 Hypertension
 Cardiac arrythmias and stroke.
 Patients must therefore be educated to avoid tyramine-containing foods.

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 Anti-histamines

An antihistamine is a type of pharmaceutical drug that opposes the activity of histamine

receptors in the body.
Classification of Antihistamines:
1) Sedative (first generation) antihistamines: Highly lipid soluble and easily enters into the
CNS:
a) Potent and marked sedative:
 Promethazine (Phenergan): widely used
 Diphenhydramine
 Dimenhydrinate
b) Potent and moderate sedative:
 Chlorcyclizine
 Chlorpheniramine
 Tetrahydroxy carboline
c) Less potent and less sedative:
 Mepyramine
 Pheniramine (avil)
2) Non-Sedative (second generation) antihistamines: Less lipid soluble therefore cannot
enter into the CNS:
 Cetirizine, Terfenadine, Loratidine

3) Antihistamines having anti-cholinergic action:

Anti-emetic and anti-motion sickness:
 Promethazine, Diphenhydramine
Anti- parkinsonism:
 Orphenadrine, Phenindamine
4) Anti-histamines having anti-serotonin action:
 Cyproheptadine
5) Anti-histamines having local anaesthetics property:
 Promethazine, Diphenhydramine

Haematinics

A haematinicsis a nutrient required for the formation of blood cells in the process of
hematopoiesis. The main haematinics are iron, B12, and folate. Deficiency in haematinics can
lead to anaemia. In cases of haematinics deficiency, haematinics can be administered as
medicines, in order to increase the hemoglobin content of the blood.

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Important haematinics are:
 Iron
 Vitamin B12
 Folic acid
Classification of haematinics (according to disease):
A) Drugs used in the iron deficiency anaemia:
1) Iron preparation:
a) Oral preparation
 Ferrous sulphate, Ferrous gluconate, Ferrous fumarate, Ferrous succinate, Ferrous choline
acetate, Ferrous carbonate, Ferric ammonium citrate.
b) Parenteral preparation
 Iron dextran complex, iron sorbitol, dextraferron.
2) Copper, cobalt, pyridoxine, riboflavin.
B) Drugs used in megaloblastic anaemia:
 Vitamin B12, Folic acid, Vitamin-C.

Cholinergic drugs

Nervous system:
1) Cholinergic neurons: Nerves which secrete acetylcholine on their stimulation are called
cholinergic neurons.
2) Adrenergic neurons: Nerves which secrete adrenaline and nor-adrenaline on their
stimulation are called adrenergic neurons.
Distribution:
 All the preganglionic and post ganglionic neurons of parasympathetic nervous system are
cholinergic in nature i.e. they secrete acetylcholine.
 All the preganglionic neurons of sympathetic are cholinergic in nature.
 Most of the ganglionic neurons of sympathetic nervous system are adrenergic in nature.
Exception: The post ganglionic sympathetic neurons supplied to sweat gland and cutaneous
blood vessels are cholinergic.

Cholinergic receptors: Cholinergic means "having to do with acetylcholine". The

neurotransmitter acetylcholine is released from the terminals of all preganglionic
neurons in both the sympathetic and the parasympathetic divisions of the ANS. Receptor which
have the affinity to bind with acetylcholine or other cholinergic drugs are called cholinergic
receptor. Acetylcholine binds with cholinergic receptors to produce its pharmacological
properties.

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 Types of Cholinergic receptors

There are two types of cholinergic receptors:

1. Muscarinic receptor
2. Nicotinic receptor
Muscarinic receptor: Muscarinic receptors are characterised through their interaction with
muscarine, a water-soluble toxin derived from the mushroom Amanita muscaria that causes
substantial activation of the peripheral sympathetic nervous system through its binding to
muscarinic AChRs, resulting in convulsions and even death. The muscarinic AChRs occur
primarily in the CNS and are part of a large family of G-protein-coupled receptors (‘G proteins’),
which use an intracellular secondary messenger system involving an increase of intracellular
calcium to transmit signals inside the cells. Muscarinic receptors are involved in a large number
of physiological functions including heart rate and force, contraction of smooth muscles and the
release of neurotransmitters.
Nicotinic receptor: Nicotinic receptors are characterised through their interaction with nicotine
in tobacco. The nicotinic AChRs are ligand-gated ion channels that form pores in cells’ plasma
membranes, mediating fast signal transmission at synapses. Nicotinic AChRs are involved in a
wide range of physiological processes and can be either neuronal or muscle-type. Muscle-type
nicotinic AChRs are localised at neuromuscular junctions, where an electrical impulse from a
neuron to a muscle cell signals contraction and is responsible for muscle tone; as such these
receptors are targets for muscle relaxants. The many types of neuronal nicotinic AChRs are
located at synapses between neurons such as in the CNS where they are involved in cognitive
function, learning and memory, arousal, reward, motor control and analgesia.
Distribution of cholinergic receptors:
 Muscarinic receptors are present/ distributed in smooth muscle, cardiac muscle, exocrine
glands and brain.
 Nicotinic receptors are distributed in autonomic ganglia, adrenal medulla and skeletal
muscles.

Cholinergic drugs

Cholinergic drugs are the agents which-

a) Have pharmacological properties similar to acetylcholine.
Or
b) Can potentiate the pharmacological activities of acetylcholine.
Or
c) Can stimulate the cholinergic neurons to secrete acetylcholine.

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 Classification of cholinergic drugs:
Cholinergic drugs can be broadly classified into three groups they are:
1) Choline esters:
 Acetylcholine, Methacholine, Carbachol, Bethanecol.

2) Natural cholinomimetic alkaloids:

 Pilocarpine, Arecoline, Muscarinic, Nicotine.

3) Anti-cholinesterase agents: It can be subdivided into three groups they are-

i. Natural- e.g. Physostigmine.

ii. Synthetic- e.g. Neostigmine, Endrophonium, Pyridostigmine.
iii. Organophosphorus compounds-
a) Alkyl-phosphate group:
 TEPP (tetra- ethyl pyro-phosphate).
 HETP (hexa-ethyl tetra-phosphate).
 DFP (di-isopropyl fluro-phosphate).
 OMPA (octa methyl pyrophosphate amide).
b) Aryl group:
 Chlorothion, Malathion, Parathion, Diazinon.
Clinical uses of cholinergic drugs (or muscarinic agonist):
 Treatment of glaucoma (Pilocarpine eye drop).
 Urinary bladder atony (Carbachol).
 Supraventricular disease (Methacholine).
 Cerebrospinal disease (Arecoline).
 After bowel surgery.
Contraindication of cholinergic drugs (cholinesters):
 Bronchial asthma, Peptic ulcer disease, Myocardial infarction, Hyperthyroidism,
Obstructive urinary retention, Mechanical obstruction of the GIT.
Adverse effects of cholinergic drugs:
 Hypotension, Bronchospasm, Cardiac arrhythmia, Bradycardia, Salivation, Lacrimation.

Anti-cholinergic drugs

Drugs which block the pharmacological actions of cholinergic drugs are called anti-cholinergic
drugs.

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Classification of Anti-cholinergic drugs:
1. Anti-muscarinic drugs
2. Anti-nicotinic drugs
a) Neuromuscular blockers
b) Ganglionic blockers

Choline esters

Choline esters are the cholinergic compound having ester linkage of choline with either acetic
acid or carbamic acid. There are four important choline esters which are used as drugs. They are-
Acetylcholine, Methacholine, Carbachol and Bethanecol.
Types of choline esters (ChE):
1. Acetylated choline esterase (true ChE):
 True ChE is present in synaps, neuro muscular junctional area, autonomic ganglion, RBC
and placenta.
 It causes hydrolysis of Ach.
2. Pseudo- choline esterase:
 Pseudo choline esterage is present in plasma, liver and GIT.
 It is responsible for transport of electrolyte and other substances in the cell membrane.

Anti-cholinesterase (Ch-E inhibitor)

Drugs which inhibit the enzyme cholinesterase and so increase the cholinergic activity are called
anti-cholinesterase.
 Anti-ChE inhibits the enzyme cholinesterase.
 Prevents hydrolysis of acetylcholine
 Increase acetylcholine concentration at cholinergic drugs sites.
So, Anti- ChE are called indirectly acting cholinergic drugs.
Types of Anti-ChE:
Reversible Anti-ChE Irreversible Anti- ChE
 Physostigmine Organophosphorus compounds.
 Neostigmine
 Pyridostigmine  DFP, TEPP, HETP
 Endrophonium  Malathion
 Parathion, Diazenon

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Mechanism of action of Anti-cholinesterase (AchE):

Anti-cholinesterase (AchE)

Inhibit cholinesterase enzyme

Prevent hydrolysis of acetylcholine

Increase acetylcholine concentration

Increase acetylcholine activity

Adrenergic drugs (sympathomimetic drugs)

Adrenergic drugs are the agents-

 Which have pharmacological properties similar to adrenaline or nor-adrenaline, or
 Which can potentiate the activities of adrenaline and nor-adrenaline, or
 Which can stimulate the sympathetic division of nervous system which release adrenaline
and nor-adrenaline.
 Adrenergic drugs can bind with either ∝-receptor or 𝛽-receptor to produce their
pharmacological effects.

Classification of Adrenergic drugs

According to therapeutic uses adrenergic drugs can be classified into four groups:
1. Vasoconstriction- e.g. Adrenaline, or nor-adrenaline.
2. Vasodilators- e.g. Dopamine, Isoprenaline
3. Bronchodilators- e.g. Salbutamol, Terbutaline.
4. CNS stimulants and anorexiants- e.g. Amphetamine, Methamphetamine.
According to mode of action adrenergic drugs can be classified into three groups:
1. Direct acting:
 Adrenaline, Noradrenaline, Isoprenaline, Dopamine.
2. Indirect acting:
 Tyramine, Amphetamine, Methamphetamine, Mephentamine.
3. By both mechanism:
 Ephedrine, Metaraminol.

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According to receptor selectivity:
1. ∝1 – agonist:
 Phenylephrine, Methoxamine.
2. ∝ 2- agonist:
 Clonidine, ∝- methyl noradrenaline.
3. Both ∝ 1−∝ 2 agonist:
 Adrenaline, Noradrenaline.
4. 𝛽1 agonist:
 Prenalterol, Dobutamine.
5. 𝛽2 agonist:
 Salbutamol, Terbutaline, Orciprenaline, Ephedrine.
6. Both 𝛽1 − 𝛽2- agonist:
 Adrenaline, Isoproterenol.
7. Both ∝ −𝛽 agonist:
 Adrenaline, Ephedrine.
Indications of adrenergic drugs:
 Bronchial asthma.
 Severe allergic reaction or anaphylactic shock.
 Hypoglycemic or hypotensive shock.
 Stokes Adams.
 Inhibition of uterine contractions.
 For vasoconstrictive and hemostatic purposes.

Contraindications of adrenergic drugs:

 Cardiac dysrhythmias, angina pectoris

 Hypertension
 Hyperthyroidism
 Cerebrovascular disease
 Distal areas with a single blood supply such as fingers, toes, nose and ears
 In renal impairment use caution

Mechanism of action of Salbutamol (𝜷 agonist):

Salbutamol (𝛽 agonist)

Stimulate 𝛽2 receptor in bronchus

↑cAMP

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 Bronchodilation

Sedative and hypnotics (minor tranquilizer)

Sedative: Drugs that reduce anxiety, excitement and exert a calming effect without affecting the
mental functions.
Hypnotics: Drugs that produce hypnosis (a state: resembling normal sleep).
Hypnosis: Hypnosis is a subconscious condition in which the objective manifestations of the
mind are more or less inactive, accompanied by abnormal sensitivity.
Progressive grade of CNS depression:
Sedation
Hypnosis
Narcosis
General anaesthesia
Coma
Death
Progressive grade of CNS excitation:
Mild hyper-excitability
Severe hyper-excitability
Mild convulsion
Severe convulsion

Classification of hypnotics

A) Barbiturate hypnotics:
1. Long acting barbiturates (8-12 hours).
 Barbitone , Phenobarbitone, Mephobarbitone , Apobarbitone.
2. Intermediate acting barbiturate (6-8 hours).
 Amilo-barbitone, Allo-barbitone, Buto-barbitone, Vin-barbitone.
3. Short acting barbiturate (3-6 hours).
 Pento-barbitone, Quinal-barbitone, Seco-barbitone.
4. Ultra- short acting (1/2-3 hours duration).

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  Thiopental Na+, Hexobarbitone Na+.

B) Non-barbiturate hypnotics:
1. Organic group:
a) Benzodiazepines (best hypnotic).
 Nitrazepam, Diazepam, Oxazepam, Temazepam.
b) Aldehyde derivatives.
 Paraldehyde.
c) Alcohol
 Ethyl alcohol, Chloral hydrate.
(Chloral hydrate used for children as hypnotics).
d) Carbamet derivatives
 Ethinmate, Urethane.
e) Piperidine derivatives
 Gluthemide, Thalidomide.
f) Miscellaneous
 Antihistamine, Scopolamine.
2. In-organic group:
 Na+ bromide, K+ bromide, NH4 bromide.
Clinical use of Sedative and hypnotics:
 To relief anxiety and tension.
 For hypnosis.
 Sedation and amnesia before medical and surgical procedure.
 In the treatment of epilepsy and seizure.
 Pre-medication prior to anaesthesia.
 For muscle relaxation.
 Diagnostic aids or for the treatment in psychiatry.
Differences between benzodiazepines and barbiturates:
BDZs (Diazepam) Barbiturates
Less pronounced CNS depressant action, More pronounced CNS depressant action,
relatively selective. non-selective CNS depressant.
Benzodiazepines are not general neuronal Barbiturates also depress general neurons
depressant
Therapeutic index high; so more safer Less therapeutic index; so not safe
Relatively safer in overdose Acute overdose causes serious cardio-
respiratory depression, coma and ends in
death

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 Less hangover Marked hangover
Slowly developing tolerance Develops rapid tolerance due to enzyme
induction
Less addiction liability Addiction liability is greater

Mechanism of action of benzodiazepines:

Benzodiazepines

Binds with specific regulatory site on GABA receptor in brain

Enhance GABA activity

Opening Cl channels

Hyperpolarization of cells

Depression of CNS

Anaesthetics
Anaesthesia: Reversible loss of sensation and consciousness is called anaesthesia.
Anaesthetics: Anaesthetics are the agents that induce loss of pain and sensation along with loss
of reflexes.
Properties of an ideal anaesthetic:
 Should induce anaesthsia smoothly.
 Permits rapid induction and rapid recovery.
 Should have a wide margin of safety.
 Should be devoid of adverse effects.
Types of anaesthetics:
1. Local anaesthetics (L.A)
2. General anaesthetics: (G.A)

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 Local anaesthetics

A local anesthetic is a medication that causes reversible absence of pain sensation, although
other senses are often affected, as well. Also, when it is used on specific nerve pathways,
paralysis also can be achieved.
Properties of an ideal local anaesthetic:
 Its actions must be reversible.
 It should be nonirritating to the tissue.
 It should not produce any local reactions.
 It should be rapid in action.
 It should have a low degree of systemic toxicity.
 It should have sufficient potency to provide complete local anesthesia.
 It should have sufficient penetrating properties.
 It should not produce allergic reactions.
 It should have high therapeutic ratio.
 It should be combined with other agents.
 It should be stable in light.
 It should not produce any permanent damage.
 Effective in body pH.
 Cheap and available.
 Rapid onset of action (as short as possible).
 Water soluble and sterilized by heat.

Classification of local anaesthetics:

A) According to duration of action.
1. Short acting (30 to 60 minutes).
 Procaine (30 min), Amethocaine (1 hour).
2. Intermediate acting (60 to 120 minutes).
 Lidocaine (lignocaine, xylocaine 1 to 1.5 hour), Articaine, Pilocaine (2 hour),
Mepivacaine.
3. Long acting (> 2 hours).
 Bupivacaine (3 hours), Tetracaine, Etidocaine, Dibucaine (3 hours).
B) According to chemical structure:
1. Ester group:
 Cocaine, Benzocaine, Tetracaine, Procaine.
2. Amide group
 Lidocaine, Prilocaine, Etidocaine, Bupivacaine.
C) According to the clinical use:
1. Surface anaesthesia:

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  Lignocaine, Cocaine, Ethylchloride.
2. Infiltration anaesthesia:
 Lignocaine, Cocaine,Procaine.
3. Nerve block anaesthesia:
 Lignocaine, Procaine, Tetracaine.
4. Spinal anaesthesia:
 Lignocaine, Procaine, Tetracaine.
5. Epidural anaesthesia:
 Lignocaine,Tetracaine., Bupivacaine.
Mode of action of local anaesthesia:
Displacement of Ca ions from the Na channel receptor site

Binding of the local anesthetic molecule to this receptor site

Blockade of the sodium channel

Decrease in sodium conductance

Decrease of the rate of electrical depolarization.

Failure to achieve the threshold potential level.

Lack of development of propagated action potentials.

Conduction blockade.

General anaesthetics

General anaesthesia or general anesthesia is a medically induced state of unconsciousness with

loss of protective reflexes along with adequate muscle relaxation.
Properties of an ideal general anaesthetic:
For the patient:
 Rapid and pleasant induction.

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  Rapid and eventual recovery.
 Non-irritant, non-inflammatory and non-explosive.
 Should not have adverse and withdrawal effect.
For the surgeon:
 Adequate muscle relaxation.
 Good analgesia.
 Does not cause capillary bleeding.
For the anaesthesiologist:
 Wide range of safety.
 Easy recovery.
For manufacturer:
 Should not decompose when stored for a long time.
 Cheap and available.
Stages of GA.:

1-Stage I: Stage of induction or analgesia.

2-Stage II: Stage of excitement or delirium (Dilated reactive pupil).

3-Stage III: Stage of Surgical anesthesia (Normal pupil). It is divided into 4 Planes.

4-Stage VI: Stage of medullary paralysis (Dilated non-reactive pupil).

Classification of GA.:

Inhalation I.V

1. Ultra short barbiturates

2. Non- barbiturates

Gases Volatile liquid Benzodiazepines, Propofol

Nitrous Halothane, Enflurane Ketamine, Etomidate, Propanidid

Oxide (N2O) Isoflurane, Desflurane Neurolept analgesia
Methoxyflurane, Trichloro-ethylene
Ethylchloride, Ether (obsolete)
Chloroform (obsolete)

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 Anticoagulants

Anticoagulants are a class of drugs that work to prevent blood coagulation or which prolong the
clotting time.
Drugs in class: Heparin, Warfarin, Dalteparin sodium, Bivalirudin, Argatroban, Lepirudin,
Heparin Sodium, Heparin/Dextrose.
Indication of Anti-coagulant therapy:
 Establish venous thromboembolism.
 Secondary prophylaxis of venous thrombosis and pulmonary embolism.
 Prosthetic heart value.
 Rheumatoid mitral valvular disease.
 Myocardial infarction (atrial fibrillation).

Contraindication of Anti-coagulant therapy:

 Haematological: Pre-existing bleeding disorder.
 Neurological: stroke within 3 weeks, surgery to brain, eye.
 CVS: severe uncontrolled hypertension.
 Alimentary: active peptic ulcer, IBS, oesophageal varices.
 Kidney: Renal failure.
 Liver: cirrhosis.
 Pregnancy: (warfarin).

Anti-diabetic drugs

According to WHO, around 100 million of people are patients of diabetes in the world.
Diabetes: Definition from WHO:
Diabetes mellitus is a metabolic disorder of multiple etiology which is characterized by chronic
hyperglycemia with disturbance of carbohydrate, fat, and protein metabolism resulting from
defects of insulin secretion, insulin action or both.
Effects of diabetes:
 Long term damage.
 Dysfunction.
 Failure of different organ.
Causes:
 Impaired glucose intake by skeletal muscle.
 Impaired glycogenesis.
 Impaired hepatic output of glucose.

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  Impaired input of glucose.
Symptoms of diabetes:
 Thirst
 Polyuria
 Weight loss
 Blurred vision
 Develop ketoacidosis because of fat breaking.
 Non ketonic hyperosmolar state will increase. This will lead to coma, if untreated it leads
to death.
Classification of Diabetes Mellitus:
Type- 1 Diabetes Mellitus: Insulin dependent diabetes mellitus or juvenile diabetes. It results
from pancreatic beta cell destruction and severe in insulin deficiency. It occurs mostly in juvenile
but occasionally at adults, especially the non-obese.
Type- 2 Diabetes Mellitus: Non-Insulin dependent diabetes mellitus, occurs in adult. It is
characterized by tissue resistance to the action of insulin combined with relative deficiency of
insulin. Although insulin is produced by beta cell it is inadequate to overcome the resistance and
blood glucose rises.
Some other types of diabetes:
 MRDM: Malnutrition Related Diabetes Mellitus.
 GDM: Gestational Diabetes Mellitus.
Treatment:
 Many complications of diabetes can be prevented or delayed through effective management.
This includes-
 Healthy diets.
 Physical activity.
 Avoidance of over weights and obesity.
 Not smoking.
 Diabetes therapy is not only about lowering glucose level but also about the overall
complications such as blood pressure and blood lipids. This requires life long care and
management.
 People with type-2 diabetes often require oral drugs and sometimes insulin is used to control
their blood levels.
 People with type-1 diabetes require insulin to survive.

Insulin
Insulin derived from Latin word “insula” means an island. Insulin is a small protein which
contains two chains (A and B) linked by disulfide bridges. Insulin is released from pancreatic

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Beta cells at a low basal rate and at much higher stimulated rate in response to a variety of
stimuli, especially glucose.
Chemistry of insulin: It consists of two open poly-peptide chains (A and B). There are 21
amino acids in chain A and 30 amino acids in B chain. Two chains are inter-linked by a di-
sulfide bridge. There is an additional di-sulfide bridge between the 6th and 11th amino acids
residues of the A chain. Breaking the di-sulfide bridge, inactivate insulin. It is protein in nature.
Its MW is 5800.

Mechanism of action of insulin:

 Insulin binds to insulin receptors on the plasma membrane and activates tyrosine kinase –
primarily in adipose tissue, liver and skeletal muscle.
 The Nerves, RBC’s, Kidney and Lens of the eye do not require insulin for glucose transport.
Liver:
 Insulin increases the storage of glucose as glycogen in the liver.
 It inserts the GLUT-2 glucose transport molecule in the cell membrane.
 It inhibits gluconeogenesis – thus significantly decrease glucose output by the liver.
 It decreases the protein catabolism.
Muscle:
 Insulin stimulates the glycogen synthesis and protein synthesis.
 Glucose transport into the cells is facilitated by GLUT-4 into the cell membrane.
 It inhibits the protein catabolism.
Adipose tissue:
 Insulin facilitates the storage of triglyceride by activating plasma lipoprotein lipase and
inhibiting intracellular lipolysis.
 It increase the glucose uptake by GLUT-4 insertion into the cell membrane.

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Classification of insulin:
 Rapid acting insulin: Lispro, Aspart and Glulisine.
 Short acting insulin: Regular (crystalline).
 Intermediate acting insulin: NPH (isophane) and Lente (insulin zinc).
 Long acting insulin: Ultralente, Detimir and Glargine.
Pharmacokinetics of insulin:
 Route of administration: Subcutaneous, IV, IM. (Orally insulin is digested because it
is protein in nature. For this reason insulin is not given orally).
 Absorption: slow in subcutaneous.
 Metabolism: Liver 60%, Kidney 40%.
 Plasma half-life: 3 – 9 minutes.
 Excretion: Urine.
Adverse effects of Insulin:
 Hypoglycemia, Allergic reactions, Lipodystrophy.
 Others includes: Seizures, Coma.

Anti- diabetic drugs

Hyperglycemia: Hyperglycemia is a condition in which blood sugar increases above the normal
level, i.e. above 120mg per 100ml. When the blood sugar level exceeds the renal threshold, sugar
appears in the urine. It mainly occurs dueto the-
 Impaired glucose intake by skeletal muscle.
 Impaired glycogenesis.
 Impaired hepatic output of glucose.
 Impaired input of glucose.

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Hypoglycemia: Hypoglycemia is a condition in which blood sugar decreases below the normal
level, i.e. below 40mg per 100ml. The symptoms-
 Sweating, Anxiety, Dizziness, Headache, Weakness, Fall in blood pressure.
Glycosuria: It is the condition when the glucose reuptake by the kidney is impaired. In this
condition blood glucose level exceeds 80mg glucose per 100ml of blood.
Hypoglycemic agent: Hypoglycemic agents that are used in the treatment and prevention of
diabetes mellitus. They are capable of reducing blood sugar level that are called hypoglycemic
agents.
Classification of anti-diabetic drugs:
1. Insulin
2. Alpha-glucosidase inhibitors (starch inhibitors)
3. Sulfonylureas
4. Biguanides
5. Thizoladinediones
6. Insulin secretagogues

Alpha-glucosidase inhibitors (starch inhibitors) – Block intestinal starch absorption– Acarbose

Miglitol

Sulfonylureas
 Glimepiride
 Glyburide
 Chlorpropamide
 Acetohexamide
 Olipazide
 Glyburide
 Tolbutamide
 Tolazamide
 Acute release of insulin by functioning beta cells of pancreatic islet tissue
 Increase insulin sensitivity
 Liver, Muscle, Fat
 RBCs, Monocytes

Biguanides
Metformin hydrochloride
 Reduces hepatic glucose overproduction
 Increases insulin receptors
 Decreased intestinal absorption of glucose

Thizoladinediones
 Piglitazone
 Rosiglitazone
 Affects Liver, Muscle, and Fat

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 Decreases insulin resistance
 Increases glucose uptake
 Decreased hepatic glucose production
 Affects PPARs (peroxizome proliferated activated receptors) – creates liver side effects

Insulin secretagogues – nonsulfonylurea hypoglycemic agents (metglitinides)

 Repaglinide
 Nateglinide (not approved in US)
 Enhances insulin secretion by functioning pancreas

Antibiotics

Antibiotics: Generally we can define Antibiotics as any chemical substances produced by

microorganism or made synthetically or semi synthetically, capable of destroying or inhibiting
the growth of other microbes specially Bacteria, Fungus etc.
Mechanism of Action:
Antibiotics mainly acts by the following four steps:
1. Inhibition of cell wall synthesis.
2. Alteration of permeability of cell membrane.
3. Inhibition of protein synthesis (Transcription, Translation).
4. Inhibition of nucleic acid synthesis
Chemotherapeutics:
Chemotherapeutics are the synthetic chemicals used to destroy or remove the infective agents
(Bacteria, Viruses, Fungi, Protozoa, and Helminths) without affecting the host tissue.
These are active against the malignant cells. Some chemotherapeutics shows antibiotic action but
not all.
Differences between Antibiotics and Chemotherapeutics:
Antibiotics Chemotherapeutics
The source of antibiotics are natural, synthetic These are usually synthetic drugs.
or semi synthetic.
Indicated in the bacterial infection. Indicated in the parasitic infection.
These are active against microbial cells. These are active against malignant cells.
All antibiotics are chemotherapeutics Some chemotherapeutics are antibiotics, but
not all chemotherapeutics are antibiotics.

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A. Narrow spectrum
Chemotherapeutic agents acting only on a single or a limited group of microorganisms are said
to have a narrow spectrum. For example, isoniazid is active only against Mycobacteria.
B. Extended spectrum
Extended spectrum is the term applied to antibiotics that are effective against gram-positive
organisms and also against a significant number of gram-negative bacteria. For example,
ampicillin is considered to have an extended spectrum because it acts against gram-positive and
some gram-negative bacteria.
C. Broad spectrum
Drugs such as tetracycline and chloramphenicol affect a wide variety of microbial species and
are referred to as broad spectrum antibiotics. Administration of broad spectrum antibiotics can
drastically alter the nature of the normal bacterial flora and can precipitate a superinfection of an
organism, such as candida whose growth is normally kept in check by the presence of other
microorganisms.

Classification of Antibiotics

Antibiotics or anti-microbial agents can be classified in different categories:

 On the basis of chemical structure.
 On the basis of the type of microorganism.
 On the basis of mechanism of action.
 On the basis of spectrum activity.
 On the basis of the type of action.

On The Basis of Chemical Structure:

 Sulphonamides and related drugs: Sulfomethoxazole.
 Diaminopyrimidine Group: Trimethoprim.
 β- lactam antibiotics: Penicillin, Cephalosporin.
 Tetracyclines: Oxytetracycline, Doxycycline.
 Nitrobenzene Derivatives: Chloramphenicol.
 Aminoglycosides: Streptomycin, Neomycin, Gentamycin.
 Macrolide antibiotics: Erythromycin, Azithromycin.
 Polypeptide antibiotics: Polymyxin-β, Bacitracin.
 Nitrofuran Derivatives: Nitrofurantoin, Furazolidone.
 Nitromidazoles: Metronidazole, Tinidazole.
 Quinolones: Ciprofloxacin, Norfloxacin.
 Polyene antibiotics: Nystatin.

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On The Basis of Type of Organisms:
 Antibacterial: Penicillin, Erythromycin.
 Antifungal: Griseofulvin, Amphotericin-β.
 Antiviral: Acyclovir.
 Antiprotozoal: Metronidazole, Chloroquine.
 Anthelmentics: Mebendazole, Albendazole.
On The Basis of Mechanism of Action:
1. Agents that inhibit the synthesis of bacterial cell wall: Penicillin (β- lactam), Vancomycin,
Cycloserine.
2. Agents that acts directly on the cell membrane and cause leakage of the cell intracellular
compounds: Polymyxin, Nystatin etc.
3. Agents that disrupt the function of 30s and 50s ribosomal subunits and reversibly inhibits the
function of protein synthesis: Tetracycline, Chloramphenicol.
4. Agents that bind with 30s ribosomal subunit and alter the protein synthesis: Aminoglycoside,
Streptomycin etc.
5. Agents that affect the bacterial nucleic acid metabolism or inhibit RNA polymerase or inhibit
topoisomerase: Ciprofloxacin.
6. Agents that block essential enzymes of folate metabolism (Dihydro folate synthatase,
Tetrahydro folate synthatase): Sulfa drugs, Sulfonamaides, Trimethoprim etc.
On The Basis of Spectrum Activity:
 Narrow spectrum: Penicillin, Streptomycin.
 Intermediate or extended spectrum: Penicillin, Newer Cephalosporin, Aminoglycoside.
 Broad Spectrum: Tetracycline, Chloramphenicol.
On The Basis of type of Action:
1. Bacteriostatic: A drug that temporarily inhibit the growth of microorganism is called
bacteriostatic. Example: Sulphonamides, Erythromycin, Chloramphenicol.
2. Bactericidal: A drug that can cause the death of microorganism is called bactericidal.
Example: Penicillin, Vancomycin, Cephalosporin.

Problems that arise with the use of Anti-microbial Agents (AMAs)

Toxicity:
a. Local irritation: This is experienced at the site of administration. Gastric irritation, pain,
abscess formation at the site of intramuscular injection. Practically all AMAs, especially
erythromycin, tetracyclines, certain cephalosporin and chloramphenicol are irritants.
b. Systemic toxicity: Practically all AMAs produce dose related and predictable organ
toxicities are exhibited by different AMAs.

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 High Therapeutic Index: The Drug with high TI, dose over nearly 100 fold range may be
given without apparent damage to host cells. It includes Penicillin, erythromycin and some
cephalosporin.
 Lower Therapeutic Index: The dose of these drugs should be individualized and toxicity
observed. For example-
Aminoglycosides: 8th cranial nerve and kidney toxicity.
Tetracyclines: Liver and kidney damage.
Chloramphenicol: Bone marrow depression.
Very Low Therapeutic Index: The use of these drugs are highly restricted to conditions where no
suitable alteration is available. For example-
Polymixin β: Neurological and renal toxicity.
Vancomycin: Hearing loss, kidney damage.
Amphotericin B: kidney, bone marrow and neurological toxicity.
Hypersensitivity Reaction:
All the AMAs are capable of causing hypersensitivity reaction. These are unpredictable and
unrelated to dose. The whole range of reactions rashes to anaphylactic shock can be predictable.
For example- Penicillins, Sulfonamides.
Drug Resistance:
Antimicrobial resistance refers to the unresponsiveness of a microorganism to an anti-microbial
agents.
Susceptible bacteria can acquire resistance to antibiotic by genetic mutation or by accepting
antimicrobial resistant genes by other bacteria. This is usually occurs by several biochemical
reaction such as
1. Mutation (Alteration of DNA).
2. Destruction or Inactivation.
3. Efflux.
4. Genetic Transfer (Infection Resistance).
Prevention of Drug Resistance:
1. No indiscriminate and inadequate or prolonged use of AMAs should be made.
2. Prefer rapidly acting and selective (Narrow spectrum) AMAs whenever possible. Broad
spectrum drugs should be used only when a specific one cannot be determined.
3. Use combination of AMAs whenever prolonged therapy is undertaken e.g. tuberculosis.

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 4. Infection by organisms notorious for developing resistance e.g. E. coli, Staphylococcus
aureus, Micobacterium tuberculosis etc. must be treated intensively.
Super Infection:
The term “Super Infection” usually refers to the appearance of a new infection as a result of
antimicrobial therapy. Use of most AMAs cause some alteration in the normal microbial flora of
the body.
To minimize super infection following attempts should be taken….
1. Use of specific (Narrow spectrum) AMA wherever possible.
2. Antimicrobials should not be used in the treatment of trivial, self-limiting or untreatable
(Viral) infections.
3. Unnecessary prolonged antimicrobial therapy should be avoided.

Choice of an Anti-Microbial Agent

Patients Factor:
Patients factor in the choice of an anti-microbial agent includes-
1. Age: Different antibiotics are efficient in different age. Conjugation and excretion of
chloramphenicol is inefficient in the new born, larger doses may produce gray baby
syndrome.
2. Renal & Hepatic function: Dose reduction is needed in renal failure. Amino glycoside,
cephalosporins, metronidazole, cortimoxazole should be avoided in renal failure.
Antimicrobials should be avoided or dose should be reduced at liver disease. Erythromycin,
tetracycline, cephalosporin should be avoided and the dose of chloramphenicol and
metronidazole should be reduced.
3. Local Factors: The condition prevailing at the site of infection greatly affect the action of
AMAs.
4. Drug Allergy: If a drug causes allergic reaction, it should be avoided to that patients.
5. Pregnancy: All AMAs should avoided during pregnancy because they have the ability to pass
through the Placental barrier and causes harm to the fetus.
6. Genetic Factors: Primaquine, Nitrofurantoin, Sulphonamides, Chloramphenicol and
Fluoroquinolones are likely to produce hemolysis in G-GPD (glucose-6-phospate
dehydrogenase) deficient patient.

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 𝜷-Lactam Drugs

 Some bacteria produce 𝛽-lactamase enzyme that breaks the critical b-lactam ring.
 𝛽-lactam drugs include: penicillins and cephalosporins.

Penicillin: In 1928 Sir Alexandar Fleming discovered penicillin. In 1940, Chain, Folery and
their associates produced significant quantity of penicillin from Penicillium notatum. It is one of
the group of β- lactam antibiotics. They are lipid insoluble and cannot cross the Blood Brain
Barrier but can pass through the placental barrier. For this reason, Penicillin is contraindicated to
pregnant women and lactating mothers.
Source:
Natural Source: Penicillium notatum (Previously used), Penicillium chrysogenum (Recently
used).
 Semi-synthetic
 Synthetic
Classification Penicillin:
A. According to the source:
1. Natural Penicillin:
 Oral: Phenoxy Methyl Penicillin or Pen-V
 Parenteral: Benzyl Penicillin or Pen-G
2. Semi-synthetic Penicillin:
a. Narrow Spectrum Penicillin:
 Oxacillin, Cloxacillin, Flucloxacillin, Dicloxacillin.
b. Broad Spectrum Penicillin:
 Ampicillin, Amoxacillin, Hetacillin.

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 c. Newer Peniicllin:
 Mezlocillin, Penamecillin, Piperacillin.
B. According to the duration of action:
1. Short acting Penicillin(4-6 hours):
 Ampicillin, Amoxacillin, Penicillin-V, Penicillin-G, Hetacillin.
2. Long Acting Penicillin:
 Benzyl Penicillin, Benethamine Penicillin, Procaine Penicillin.
Pharmacokinetics:
 Route of Adminstration: Oral, Parenteral (IV, IM).
 Distribution: Widely distribution.
 Plasma Half Life: Usually less than 2 hours.
 Elimination: Mainly renal and rapidly occurs.
Uses of Penicillin:
Disease Organism Drug
Bacterial meningitis Neisseria meningitides Benzyl penicillin
Bone and joint infection Staphylococcus aureus Flucloxacillin
Skin and soft tissue infection Streptococcus pyrogens Benzyl penicillin,
Flucloxacillin
Pharyngitis Streptococcus pyrogens Penicillin- V
Urinary tract infection E. coli Amoxicillin
Gonorrhoea Neisseria gonorrhoea Amoxicillin+ probenecid+
Other antibiotics
Endocarditis Streptococcus viridans Benzyl penicillin+
Aminoglycoside

Unwanted Effect of Penicillin:

1. Hypersensitivity Reaction:
Immediate type:
 Anaphylactic Shock: Bronchospasm, Hypertension.
 Skin rash, fever.
 Interstitial nephritis.

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Delayed Type:
Urticaria, fever, Joint swelling, Pruritis.
2. GIT upset:
 Loose motion, Nausea, Vomitting.

Cephalosporin
Cephalosporins are a class of β- lactam antibiotics originally derived from Acremonium, which
was previously known as “Cephalosporium”.
Classification of Cephalosporin:
Cephalosporins are divided into five classes:
1. First Generation: It is active against gram (+ve) positive bacteria.
Parenteral:
Cephalothin, Cephradine, Cefazolin.
Oral:
 Cephradine, Cephalexin, Cefadroxil.
2. Second Generation: It is active against gram (-ve) negative bacteria.
Parenteral:
 Cefamandole, Cefoxitin.
Oral:
 Cefaclor, Cefauroxim.
3. Third Generation: It is active against gram (-ve) negative bacteria but has less activity
against gram (+ve) positive bacteria.
Parenteral:
 Cefotaxime, Moxalactam, Ceftriaxone, Cefoperazone.
Oral:
 Cefixime
4. Fourth Generation: It is active against gram (-ve) negative bacteria and also effective
against streptococci and staphylococci.
 Cefepime, Cefpirome
5. Fifth Generation: It is extended spectrum antibiotics.
 Ceftobiprole, Ceftaroline fosamil

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Indications of cephalosporin:
 Urinary tract infection (oral cephalosporins), Infections of the gut (enterobacteria),
Respiratory tract infection (H. influenzae), Boils, abscess, Prophylaxis in surgery, Biliary
sepsis, Person allergic to penicillin, Meningitis (resistant case), Gonorrhoea (penicillin
resistant), Infected burns, Septicaemia, Aspiration pneumonia.
Adverse effects of cephalosporin:
 Allergy, Anaphylaxis, Fever, Skin rash, Nephritis, Granulocytopenia, Haemolytic
anaemia, Local irritation, Renal toxicity, Superinfection.
Comparision between Penicillin & Cephalosporin:
Penicillin Cephalosporin
Obtained from p. notatum and p. Obtained from Cephalosporium acremonium
chrysogenum
On hydrolysis yield 6- aminopenicillanic acid On hydrolysis yield 7- aminocephalesperinic
(6- APA) acid (7-ACA)
Less active than Cephalosporin More active than Penicillin
Natural penicillin are narrow spectrum Cephalosporin are broad spectrum antibiotics
antibiotics
Destroyed by 𝛽- lactamase Resistant to 𝛽- lactamase
Orally inactive due to acid sensitivity Relatively acid stable
Exhibit more allergenicity Exhibit less allergenicity
Both bacteristatic and bactericidal Mainly bactericidal
More toxic Less toxic

Antiviral Drugs

 Viruses are obligate intracellular parasites.

 They lack both a cell wall and a cell membrane and they do not carry out metabolic
processes.
 Viral reproduction uses much of the host's metabolic machinery and few drugs are selective
enough to prevent viral replication without injury to the host.
Classification of Antiviral Drugs:
1. For Respiratory Virus Infections:
 Amantadine, Oseltamivir, Ribavirin, Rimantadine, Zanamivir

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 2. For Hepatic Viral Infections:
 Adefovir, Entecavir, Interferon, Lamivudine, Telbivudine

3. For Herpes and Cytomegalovirus Infections:

 Acyclovir, Cidofovir, Famciclovir, Fomiversin, Ganciclovir, Vidarabine

4. For HIV Infections:

 Abacavir, Atazanavir, Enfuvirtide, Lamivudine, Nelfinavir, Raltegravir, Zidovudine

Currently Available Anti-HIV Drugs

1. Nucleoside/-tide reverse transcriptase inhibitors:
 Abacavir, Didanosine, Lamivudine, Zidovudine

2. Nonnucleoside reverse transcriptase inhibitors:

 Delavirdine, Efavirenz, Etravirine

3. Protease inhibitors:
 Atazanavir, Darunavir, Lopinavir, Nelfinavir

4. Fusion inhibitors:
 Enfuvirtide, Maraviroc

5. Integrase inhibitors:
 Raltegravir

Anti-fungal Drugs

An antifungal medication is a pharmaceutical fungicide or fungistatic used to treat and prevent

mycoses such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such
as cryptococcal meningitis and others.
Classification of anti-fungal drugs:
1. Systemic anti-fungal drugs
Oral:
 Griseofulvin, Miconazole, Ketoconazole, Flucytosine.
Parenteral:
 Amphotericin, Miconazole, Flucytosine.

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2. Topical anti-fungal drugs:
 Nystatin, Clotrimazole, Miconazole, Amphotericin, Benzoic acid and salicylic acid
(Whitfield’s ointment).
3. Both systemic and tropical anti-fungal drugs:
 Miconazole, Ketoconazole.

Amino acid

Amino acid: Amino acids are organic acid in which one or more hydrogen atoms are replaced
by amino (-NH2) group and a carboxyl (-COOH) group.
Classification of amino acid:
A. According to their functional group:
1. Neutral amino acids- mono amino- mono carboxyl acid-alanine
 Aliphatic series
 Aromatic series
2. Acidic amino acid-mono amino dicarboxyl acid. E.g: Aspartic acid
3. Basic amino acids-diamino mono-carboxylic acid. E.g: Lysine
4. Imino acids-containing imino group but no amino group. E.g: Proline
C) According to their biological value:
1. Essential amino acids
2. Semi essential amino acids
3. Non-essential amino acids
Essential amino acids: Essential amino acids are those which cannot be synthesized by the body
but needed for the growth of the body and hence they have to be supplied in the diet.

There are eight essential amino acids such as:

Threonine, Valine, Isoleucine, Phenylalanine, Metheonine, Leucine, Lysine, Thryptophen
Semi essential amino acid: Whose amino acids are partly synthesized by the body is called semi
essential amino acids.
There are two semi essential amino acids such as: Arginine, Histadine.
Non-essential amino acids: Whose amino acids are synthesized by the body is called Non-
essential amino acids.
There are ten non-essential amino acids such as:
Glycine, Alanine, Tyrosine, Serine, Asparagine, Cysteine, Aspartic acid, Proline, Glutamic acid,
Glutamine.

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 Chapter-Five

Pharmaceutics

Pharmaceutics is the discipline of pharmacy that deals with the process of turning a new
chemical entity (NCE) or old drugs into a medication to be used safely and effectively by
patients. It is also called the science of dosage form design.

Granulation

Granules: Granules are prepared agglomerates of smaller particles of powders. They are
irregular shaped but may be prepared to be spherical. Granules size ranges between 0.2 to 4.0
mm depending upon use of granules.
Reasons for granules:
 To avoid powder segregation.
 To enhance the flow property of powder.
 To produce uniform mixtures.
 To produce dust free formulations.
 To eliminate poor content uniformity.
 To improve compaction characteristics of mix.
Granulation: Granulation is the process of collecting particles together by creating bonds
between them. Bonds are formed by compression or by using a binding agent that is called
granulation.

Granulation mechanism

Particle bonding mechanisms:

To form granules bonds must be formed between powder particles so that they adhere and these
bonds must be sufficiently strong to prevent breakdown of the granules to powder in subsequent
handling operations.
There are five primary bonding mechanisms between particles:
 Adhesion and cohesion forces in the immobile liquid films between individual primary
powder particles
 Interfacial forces in mobile liquid films within the granules
 The formation of solid bridges after solvent evaporation
 Attractive forces between solid particles
 Mechanical interlocking
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Adhesion and cohesion forces in immobile liquid films: In wet granulation sufficient liquid or
highly viscous solution can form immobile thin layer results in an effective decrease in
interparticulate distance and an increase in contact area between the particles. As Vander Waals
forces of attraction are proportional to the particle diameter and inversely proportional to the
square of the distance of separation, the bond strength between the particles will be increased.
Interfacial forces in mobile liquid films: When enough liquid is applied to exceed immobile
film to mobile film, the liquid distribution between and around the particles follows, some states.
Those states are as follows:
 Pendular state
 Capillary state
 Funicular state
 Droplet
Solid bridges: These can be formed by-
 Particle melting
 Hardening binders and
 Crystallization of dissolved substances
Attractive forces between solid particles: Each particle possesses Vander Walls force and also
sometimes electrostatic force both of which contributes to cohesion and adhesion forces between
particles.
Interlocking bonds: Interlocking forces exists in granules because of having few particles cause
interlocking bonds between granules.
Mechanisms of granule formation: The formation of granules in dry and wet granulation
follows different manner. The precise mechanisms by which a dry powder is transformed in to a
bed of granules is probably different for each type of granulation equipment. But the
mechanisms discussed below, originally proposed for pan granulation has divided into three
stages:
 Nucleation: Here, the particles adhere due to liquid bridges which are the initiation step of
Granulation. These adhered particles play a role of nucleus for further enlargement of
granules.
 Transition: Enlargement of nucleus takes place by two possible mechanisms. Individual
particle adhere to the nucleus or two or more nuclei combine among themselves.
 Ball growth or enlargement of the granule.
 Coalescence: Two or more granules join to form a larger granule.
 Breakage: Granules break into fragments which adhere to other granules, forming a
layer of material over the surviving granule.
 Abrasion transfer: Agitation of the granule bed leads to the attrition of material
from granules. This abraded material adheres to other granules, increasing their size.

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  Layering: When a second batch of powder mix is added to a bed of granules the
powder will adhere to the granules, forming a layer over the surface and increasing
the granule size.

Techniques for granulation process

There are three types of techniques for granulation process:

A. Wet granulation
B. Dry granulation
C. Direct granulation

Wet granulation
Wet granulation: In wet granulation, granules are formed by the addition of a granulation liquid
onto a powder bed which is under the influence of an impeller (in a high-shear granulator),
screws (in a twin screw granulator) or air (in a fluidized bed granulator). The agitation resulting
in the system along with the wetting of the components within the formulation results in the
aggregation of the primary powder particles to produce wet granules. The granulation liquid
(fluid) contains a solvent which must be volatile so that it can be removed by drying and be non-
toxic.
Steps of wet granulation:
Requisition of raw materials

Weighing / dispensing

Crushing and sieving of all ingredients

Dry mixing

Addition of granulating fluid

Co-milling

Screening

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 Drying in Fluid bed dryer

Size reduction / dry milling

Lubrication / blending

Compression of tablet

Finished
Advantages of wet granulation:
 Improved flow by increasing particle size.
 Uniform distribution of API, colour etc. – improved content uniformity.
 Good for bulky powders, less dust and environmental contamination.
 Lower compression pressure, less wear and tear on tooling.
Disadvantages of wet granulation:
 Large number of processing steps
 More equipment
 Wetting and drying stages are time consuming

Dry granulation

Dry granulation: The dry granulation process is used to form granules without using a liquid
solution because the product to be granulated may be sensitive to moisture and heat. Forming
granules without moisture requires compacting and densifying the powders. In this process the
primary powder particles are aggregated under high pressure. Dry granulation can be conducted
under two processes; either a large tablet (slug) is produced in a heavy duty tableting press or the
powder is squeezed between two rollers to produce a sheet of materials (roller compactor,
commonly referred to as a chilsonator). Example: Aspirin tablet.
Process can be carried out in two ways:
Slugging: Large tablet produced in heavy duty tablet press.
Roller compaction: Powder is squeezed between two rollers to produce sheet of material.

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Steps of dry granulation:
Requisition of raw materials
Weighing / dispensing

Compression into slugs or roll compaction

Milling and screening of slugs

Lubrication / blending

Compression of tablet
Advantages of dry granulation:
 Improved flow by increasing particle size.
 Improved cohesion during compression.
 Granulation without addition of liquid.
Disadvantages of dry granulation:
 Possible particle segregation.
 Greater possibility of cross contamination.

Direct compression
Direct Compression: The term “direct compression” is defined as the process by which tablets
are compressed directly from powder mixture of API and suitable excipients. It involves only
two unit operations powder mixing and tableting.

Steps of direct compression:

Requisition of raw materials

Weighing / dispensing

Lubrication / blending

Compression of tablet

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Advantages of direct granulation:
 Fewer processing steps – blending and compression -reduced processing time.
 Processing without moisture and heat – fewer stability problems.
 Rapid and most direct method of tablet compression.
Disadvantages of direct granulation:
 Possibility of lot to lot variations due to differences in flow ability and moisture of
excipients.
 Higher risk of content uniformity failure in low dose products.
 Lack of moisture can create static charges that can result in un-blending.
Difference between wet granulation and dry granulation.
Wet granulation Dry granulation
Suitable solvent is used. No solvent is used.
Production cost is high. Production cost is less
It is a complex process. Very simple process.
Little chance of contamination. As water is used, contamination may be
occurred.

Methods of granulation

There are four methods of granulation:

1. High shear mixture granulation.
2. Fluid bed granulation.
3. Extrusion- Spheronization.
4. Spray drying granulation.

High shear mixture granulation

High shear mixture granulation: It has been widely used for blending and granulation, which
can be accompanied by high mechanical agitation by an impeller and a chopper. Mixing,
densification and agglomeration are achieved through shear and compaction force exerted by the
impeller.
Dry powder mixing (approx. 2-5 mins)

Liquid binder addition (approx. 1-2 mins)

Wet massing
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 Wet sieving of granules

Drying

Dry sieving of granules

Advantages and disadvantages of high shear mixture granulation.

Advantages Disadvantages
 Short processing time.  Increase in temperature may cause
 Lesser amount of liquid binders chemical degradation of thermolabile
required compared with FBG. material.
 Highly cohesive material can be  Over wetting of granules can lead to large
granulated. size lumps formation.

Fluid bed granulation

Fluid bed granulation: Fluidization is the operation by which fine solids are transformed into a
fluid like state through contact with a gas. Granulating and drying can be completed in one step
inside the machine.
Advantages and disadvantages of fluid bed granulation.

Advantages Disadvantages
 It reduces dust formation during  The Fluid Bed cleaning is labor-
processing. intensive and time consuming.
 It reduces product loss.  Difficulty of assuring reproducibility.
 It improves worker safety.  The equipment is expensive.


Extrusion- Spheronization

1. Dry mixing of materials to achieve homogeneous dispersion.

2. Wet granulation of the resulted mixture to form wet mass.

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3. Extrusion of wet mass to form rod shaped particles.
4. Rounding off (in spheronizer).
5. Drying.
Advantages of Extrusion- Spheronization:
 Extrusion/spheronization process is used to make uniformly sized spherical particles.
 It is used primarily to produce multiparticulates for controlled drug release applications.
 Ideal flow behaviour and disability.
 Compact structure.
 Low hygroscopicity
 High bulk density

Spray drying granulation

Spray drying granulation: It is a unique granulation technique that directly converts liquids
into dry powder in a single step. This method removes moisture instantly and converts pump able
liquids into a dry powder.
Advantages of spray drying granulation:
 Rapid process.
 Suitable for heat sensitive product.
 Ability to be operated continuously.

Compression

Principle: Powder/granules are pressed inside a die and compressed by two punches into required
size, shape and embossing.
Steps of compression:
Weighing

Mixing

Granulation

Screening

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 Drying

Screening

Lubrication

Compression

% Compressibility

 CARR’S INDEX

% Compressibility = (Tapped density – Bulk density/Tapped density)*100

% Compressibility Flow description

5-15 Excellent
12-16 Good
18-21 Fair to passable
23-35 Poor
35-38 Very poor
> 40 Extremely poor

Flow Properties
 HAUSNER RATIO

Hausner Ratio = Tapped Density / Bulk Density

HAUSNER RATIO Type of flow

Less than 1.25 Good flow

1.25- 1.5 Moderate
More than 1.5 Poor flow

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ANGLE OF REPOSE

Angle of repose: Maximum angle that can be obtained between a freestanding heap of powder
and the horizontal plane. It is an indication of the resistance to flow of the powder.
When only gravity acts on a static heap of powder, it tends to form a conical mound. The angle
that the sides of the heap make with the horizontal is known as the angle of repose(𝜃).
 The angle of repose is determined by allowing a powder to flow through a funnel and fall
freely onto a horizontal surface.
 The height and diameter of the resulting cone is measured and the angle of repose is
calculated using the following equation: 𝜃= tan −1(h/r). Where, h= height of the powder
cone, r = radius of the cone.
 Value for angle of repose ≤30° usually indicates a free flowing material and angles ≥40°
suggest a poorly flowing material.
Angle of repose Type of flow
<25 Excellent
25-30 Good
30-40 Passable
>40 Very poor

Angle of spatula:
 When only small quantities of powder are available, an alternative is to determine the “Angle
of spatula”.
 It is the angle that the triangular section of a powder heap on a spatula forms with the
horizontal, when a quantity of powder is picked upon it.
 This is obviously somewhat crude determination but is useful during preformation when only
small quantities of the drug available.

Dryer

Dryer: It is an equipment that is used for drying wet materials.

Classification of different types of dryer:

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1. Static bed dryers: System in which there is no relative movement among the solid particles
being dried although there may be bulk motion of the entire drying mass.
a) Tray and trunk dryer b) Tunnel and conveyor dryer

2. Moving bed dryer: System in which the drying particles are partially separated so that the
flow over each other.
a) Turbo tray dryer b) Pan dryer

3. Fluidized bed dryer: System in which the solid particles are partially suspended in an
upward moving gas stream.
a) Vertical FBD b) Horizontal FBD

4. Pneumatic dryer: System in which the drying particles are entrained and conveyed in a high
velocity gas system.
a) Spray dryer b) Flash dryer

5. Special drying methods: a) Freeze dryer b) Microwave drying

Drying

Drying: Drying is a unit operation in which a liquid is separated from a solid by other than
mechanical means. This generally requires supplying heat and resulting in evaporation of liquid.
Drying Principle:
 Migration of moisture from the interior of a material to its surface.
 Evaporation of moisture from surface to the surrounding air.
Importance of drying:
 Preparation of bulk drugs.
 Preservation of drug products.
 Improved handling.

Fluidized bed dryers

Principle of fluidized bed dryers: It is the system in which the solid particles are partially
suspended in an upward moving gas stream. In this dryer, hot air (gas) is passed at high pressure
through a perforated bottom of the container containing granules to be dried. The granules are
lifted from the bottom suspended in the stream of air. This condition is called fluidized state. The
hot gas is surrounding every granule to completely dry them. Thus materials or granules are
uniformly dried.

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Advantages of fluidized bed dryers:
 Less time (20-40 min) requires to complete drying.
 Available in different sizes with drying capacity from 5-200 kg per hr.
 Drying containers are mobile, making handling simple and reducing labor cost.
 Thermal efficiency is 2-6 times higher than tray dryer.
 Thermo labile substance (e.g. antibiotics) can be dried.
 It can be used either as batch type or continuous type.
Disadvantages of fluidized bed dryers:
 The FBD is not an explosion proof instrument and therefore samples having volatile
compounds that are flammable or able to reach their flash point should not be used with
this dryer.

Freeze drying

Freeze-drying: Freeze-drying technically known as lyophilization or cryodesiccation-is a

dehydration process typically used to preserve a perishable material or make the material more
convenient for transport. Freeze-drying works by freezing the material and then reducing the
surrounding pressure to allow the frozen water in the material to sublimate directly from the
solid phase to the gas phase.

Steps of freeze drying: Freezing

Vacuum

Primary drying / Sublimation phase

Secondary drying / Ordinary drying

Packaging

Storage

Reconstitution phase

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Application of freeze drying:
Pharmaceutical and biotechnology:
1. Pharmaceutical companies often use freeze-drying to increase the shelf life of products, such
as vaccines and other injectable.
2. By removing the water from the material and sealing the material in a vial, the material can be
easily stored, shipped and later reconstituted to its original form for injection.
Food Industry:
1. Freeze-drying is used to preserve food and make it very lightweight.
2. The process has been popularized in the forms of freeze-dried ice cream, an example of
astronaut food.
Technological Industry:
1. In chemical synthesis, products are often freeze- dried to make them more stable or easier to
dissolve in water for subsequent use.
2. In bio- separations, freeze-drying can be used also as a late-stage purification procedure,
because it can effectively remove solvents.
Advantages of Lyophilization:
 Chemical decomposition is minimized.
 Removal of water without excessive heating.
 Enhanced product stability in a dry state.
 Ease of processing a liquid, simplifies aseptic handling.
 More compatible with sterile operations than dry powder filling.
Disadvantages of Lyophilization:
 Increased handling and processing time.
 Volatile compounds may be removed by vacuum.
 Need for sterile diluents upon reconstitution.

Milling
Milling: Equipment used to reduce the particle size of solids. Solids particles present in
semisolids and suspensions can be reduced by using specially designed machine.
Advantages of milling:
 It increases surface area, which may enhance an actives dissolution rate and hence
bioavailability.
 Improved the tablet-to-tablet content uniformity by virtue of the increased number of
particles per unit weight.

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  Improved flow properties of raw materials.
 Improved colour and/or active ingredient dispersion in tablet excipients.
Disadvantages of milling:
 Excessive heat generation can lead to degradation, change in polymorphic form
 Increase in surface energy can lead to agglomeration.
 May result in excessive production of fines or overly broad particle size distribution.

Tablet

Tablet: Tablets are solid dosage forms consisting of active ingredient(s) and suitable
pharmaceutical excipients. They may vary in size, shape, weight, hardness, thickness,
disintegration and dissolution characteristics and in other aspects.
General properties of Tablet dosage forms:
 A tablet should have elegant product identity while free of defects like chips, cracks,
discoloration, and contamination.
 Should have sufficient strength to withstand mechanical shock during its production
packaging, shipping and dispensing.
 Should have the chemical and physical stability to maintain its physical attributes over
time.
 The tablet must be able to release the medicinal agents in a predictable and reproducible
manner.
 Must have a chemical stability over time so as not to follow alteration of the medicinal
agents.
Advantages of the Tablet dosage form are:
Production aspect:
 Large scale production at lowest cost
 Easiest and cheapest to package and ship
 High stability
Use aspect (doctor, pharmacist, patient)
 Easy to handle
 Lightest and most compact
 Greatest dose precision and least content variability
Disadvantages of Tablet dosage form are:
 Difficult to swallow in case of children and unconscious patients.
 Some drugs resist compression into dense compacts, owing to amorphous nature, low
density character.

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  Drugs with poor wetting, slow dissolution properties, optimum absorption high in GIT
may be difficult to formulate or manufacture as a tablet that will still provide adequate or
full drug bioavailability.
 Bitter testing drugs, drugs with an objectionable odor or drugs that are sensitive to
oxygen may require encapsulation or coating. In such cases, capsule may offer the best
and lowest cost.

Different types of Tablets

(A) Tablets ingested orally:

1. Compressed tablet, e.g. Paracetamol tablet
2. Multiple compressed table
3. Delayed release tablet, e.g. Enteric coated Bisacodyl tablet
4. Sugar coated tablet, e.g. Multivitamin tablet
5. Film coated tablet, e.g. Metronidazole tablet
6. Chewable tablet, e.g. Antacid tablet
(B) Tablets used in oral cavity:
1. Buccal tablet, e.g. Vitamin-C tablet
2. Sublingual tablet, e.g. Vicks Menthol tablet
3. Troches or lozenges
4. Dental cone
(c) Tablets administered by other route:
1. Implantation tablet
2. Vaginal tablet, e.g. Clotrimazole tablet
(D) Tablets used to prepare solution:
1. Effervescent tablet, e.g. Dispirin tablet (Aspirin)
2. Dispense tablet, e.g. Enzyme tablet (Digiplex)
3. Hypodermic tablet
4. Tablet triturates e.g. Enzyme tablet (Digiplex)

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 Tablet Ingredients

In addition to active ingredients, tablet contains a number of inert materials known as additives
or excipients. Different excipients are:
1. Diluent
2. Binder and adhesive
3. Disintegrants
4. Lubricants and glidants
5. Colouring agents
6. Flavoring agents
7. Sweetening agents

Functions of excipients

 Impart weight, accuracy, & volume (its allow accuracy of dose).

 Improve solubility.
 Increase stability.
 Enhance bioavailability.
 Modifying drug release.
 Increase patient acceptability.
 Facilitate dosage form design.

Component Function Examples

Fillers/ Increase size and weight of final dosage Microcrystalline cellulose,
Diluent form. sucrose.
Binders Promote particle aggregation. Pregelatinized starch,
hydroxypropyl
methylcellulose.
Disintegrants Promote break down of aggregates. Sodium starch glycolate.
Flow aids Reduce interaction between particles. Talc.
Lubricants Reduce interactions between particles and Magnesium stearate.
surfaces of processing equipment.
Surfactants Promotes wetting. Sodium lauryl sulfate,
polysorbate.
Modified Influences the release of active. Hydroxypropyl
release agents methylcellulose, surelease.

Diluent: Diluents are substance used to make required bulk of the tablet when the drug dosage
itself is inadequate to produce the bulk. Secondary reason is to provide better tablet properties

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such as improve cohesion, to permit use of direct compression manufacturing or to promote
flow. A diluent should have following properties:
 They must be nontoxic.
 They must be commercially available in acceptable grade.
 Their cost must be low.
 They must be physiologically inert.
 They must be physically & chemically stable by themselves & in combination
with the drugs.
 They must be free from all microbial contamination.
 They must not alter the bioavailability of drug.
 They must be color compatible.

Commonly used tablet diluents

 Lactose-anhydrous and spray dried lactose
 Directly compressed starch-Sta Rx 1500
 Hydrolyzed starch-Emdex and Celutab
 Microcrystalline cellulose-Avicel (PH 101 and PH 102)
 Dibasic calcium phosphate dehydrate
 Calcium sulphate dihydrate
 Mannitol
 Sorbitol
 Sucrose- Sugartab, DiPac, Nutab
 Dextrose
Binders and Adhesives: These materials are added either dry or in wet- form to form granules
or to form cohesive compacts for directly compressed tablet.
 Example: Acacia, tragacanth- Solution for 10-25% Conc.
 Cellulose derivatives- Methyl cellulose, Hydroxy propyl methyl cellulose,
Hydroxy propyl cellulose.
 Gelatin- 10-20% solution.
 Glucose- 50% solution.
 Polyvinylpyrrolidone (PVP)- 2% conc.
 Starch paste-10-20% solution.
 Sodium alginate.
 Sorbitol.
Disintegrants: Added to a tablet formulation to facilitate its breaking or disintegration when it
contact in water in the GIT.
 Example: Starch- 5-20% of tablet weight.
 Starch derivative – Primogel and Explotab (1-8%).
 Clays- Veegum HV, bentonite 10% level in colored tablet only.
 Cellulose.

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  Cellulose derivatives- Ac- Di-Sol (sodium carboxy methyl cellulose).
 Alginate.
 PVP (Polyvinylpyrrolidone) cross-linked.

Superdisintegrants: Swells up to ten fold within 30 seconds when contact water.

 Example: Crosscarmellose- cross-linked cellulose, Crosspovidone- cross-linked povidone
(polymer), Sodium starch glycolate- cross-linked starch. These cross-linked products swells
within 30 seconds when in contact with water.
Lubricant and Glidants: Lubricants are intended to prevent adhesion of the tablet materials to
the surface of dies and punches, reduce inter particle friction and may improve the rate of flow of
the tablet granulation.
Glidants are intended to promote flow of granules or powder material by reducing the friction
between the particles.
 Lubricants- Stearic acid, Stearic acid salt - Stearic acid, Magnesium stearate, Talc, PEG
(Polyethylene glycols), Surfactants.
 Glidants- Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative - Colloidal silicas
such as Cab-O-Sil, Syloid, Aerosil in 0.25-3% conc.
Coloring agent: The use of colors and dyes in a tablet has three purposes:
(1) Masking of odd color drugs.
(2) Product Identification.
(3) Production of more elegant product.
All coloring agents must be approved and certified by FDA. Two forms of colors are used in
tablet preparation – FD &C and D & C dyes. These dyes are applied as solution in the
granulating agent or Lake form of these dyes. Lakes are dyes absorbed on hydrous oxide and
employed as dry powder coloring.
Example: FD & C yellow 6-sunset yellow, FD & C yellow 5- Tartrazine , FD & C green 3- Fast
Green, FD & C blue 1- Brilliant Blue, FD & C blue 2 - Indigo carmine, D & C red 3-
Erythrosine, D & C red 22 – Eosin Y.
Flavoring agents: For chewable tablet- flavor oil are used
Sweetening agents: For chewable tablets: Sugar, mannitol.
 Saccharine (artificial): 500 time’s sweeter than sucrose
Disadvantage: Bitter aftertaste and carcinogenic
 Aspartame (artificial)
Disadvantage: Lack of stability in presence of moisture.

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 Tablet compression machine

Tablet compression machine: The basic principle behind the tablet compression machine is
hydraulic pressure. This pressure is transmitted unreduced through the static fluid. Any
externally applied pressure is transmitted via static fluid to all the directions in same proportion.
It also makes it possible to multiply the force as needed.
Tablet presses are designed with following basic components:
 Hopper for holding and feeding granulation.
 Dies that define the size and shape of the tablet.
 Punches for compressing the granulation within the dies.
 Cam tracks for guiding the movement of the punches.
 A feeding mechanism for moving granulation from hopper into the dies.

Tablet compression

Tablet compression: After the preparation of granules (in case of wet granulation) or sized
slugs (in case of dry granulation) or mixing of ingredients (in case of direct compression), they
are compressed to get final product. The compression is done either by single punch machine
(stamping press) or by multi station machine (rotary press).

Common stages occurring during compression:

Stage 1: Top punch is withdrawn from the die by the upper cam. Bottom punch is low in the die
so powder falls in through the hole and fills the die.

Stage 2: Bottom punch moves up to adjust the powder weight-it raises and expels some powder.

Stage 3: Top punch is driven into the die by upper cam. Bottom punch is raised by lower cam.
Both punch heads pass between heavy rollers to compress the powder.

Stage 4: Top punch is withdrawn by the upper cam. Lower punch is pushed up and expels the
tablet. Tablet is removed from the die surface by surface plate.

Stage 5: Return to stage 1.

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 Figure: Stages occurring during compression

Problems of tablet manufacturing and Remedies

Capping

Lamination
Process
Related
Cracking

Chipping

Visual Sticking
Defects
Formulation
Picking
Related

Binding

Machine Double
Related Impression

Capping

Capping: ‘Capping’ is the term used, when the upper or lower segment of the tablet separates
horizontally, either partially or completely from the main body of a tablet and comes off as a cap,
during ejection from the tablet press or during subsequent handling.
Reason: Capping is usually due to the air–entrapment in a compact during compression and
subsequent expansion of tablet on ejection of a tablet from a die.

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The causes and remedies of Capping related to ‘formulation’ (Granulation) are as follows:
Sr. CAUSES REMEDIES
No.
1. Large amount of fines in the Remove some or all fines through 100 to 200 mesh
granulation screen
2. Too dry or very low moisture Moisten the granules suitably. Add hygroscopic
content (leading to loss of proper substance e.g.: sorbitol, methyl- cellulose or PEG-
binding action). 4000.
3. Not thoroughly dried granules. Dry the granules properly.
4. Insufficient amount of binder or Increasing the amount of binder OR
improper binder. Adding dry binder such as pre-gelatinized starch,
gum acacia, powdered sorbitol, PVP, hydrophilic
silica or powdered sugar.
5. Insufficient or improper lubricant. Increase the amount of lubricant or change the type
of lubricant.
6. Granular mass too cold to Compress at room temperature.
compress firm.

The causes and remedies of Capping related to ‘machine’ (dies, punches and tablet press)

Sr. CAUSES REMEDIES

No.
1. Poorly finished dies Polish dies properly. Investigate other steels
or other materials.
2. Deep concave punches or beveled-edge Use flat punches.
faces of punches.
3. Lower punch remains below the face of Make proper setting of lower punch during
die during ejection. ejection.
4. Incorrect adjustment of sweep-off blade. Adjust sweep-off blade correctly to facilitate
proper ejection.
5. High turret speed. Reduce speed of turret (Increase dwell
time).

Lamination / Laminating

Lamination: Lamination is the separation of a tablet into two or more distinct horizontal layers.
Reason: Air-entrapment during compression and subsequent release on ejection.
The causes and remedies of lamination related to formulation (Granulation) are as follows:

Sr. CAUSES REMEDIES

No.
1. Oily or waxy materials in granules Modify mixing process. Add adsorbent or

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 absorbent.
2. Too much of hydrophobic lubricant e.g.: Use a less amount of lubricant or change
Magnesium-stearate. the type of lubricant.

The Causes and Remedies of Lamination related to MACHINE (Dies, Punches and Tablet
Press)
Sr. CAUSES REMEDIES
No.
1. Rapid relaxation of the peripheral Use tapered dies, i.e. upper part of the die
regions of a tablet, on ejection from a bore has an outward taper of 3° to 5°.
die.
2. Rapid decompression Use pre-compression step. Reduce turret
speed and reduce the final compression
pressure.

Chipping

Chipping: ‘Chipping’ is defined as the breaking of tablet edges, while the tablet leaves the press
or during subsequent handling and coating operations.
Reason: Incorrect machine settings, specially mis-set ejection take-off.

The causes and remedies of chipping related to formulation (Granulation) are as follows:
Sr. CAUSES REMEDIES
No.
1. Sticking on punch faces Dry the granules properly or increase lubrication.
2. Too dry granules. Moisten the granules to plasticize. Add
hygroscopic substances.
3. Too much binding causes chipping Optimize binding, use dry binders.
at bottom.

The Causes and Remedies of chipping related to MACHINE (Dies, Punches and Tablet
Press)
Sr. CAUSES REMEDIES
No.
1. Groove of die worn at compression Polish to open end, reverse or replace the
point. die.
2. Barreled die (center of the die wider than Polish the die to make it cylindrical
ends)
3. Edge of punch face turned inside/inward. Polish the punch edges
4. Concavity too deep to compress Reduce concavity of punch faces. Use flat
properly. punches.

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 Cracking

Cracking: Small, fine cracks observed on the upper and lower central surface of tablets or very
rarely on the sidewall are referred to as ‘Cracks’.
Reason: It is observed as a result of rapid expansion of tablets, especially when deep concave
punches are used.

The causes and remedies of cracking related to formulation (Granulation) are as follows:
Sr. No. CAUSES REMEDIES
1. Large size of granules. Reduce granule size. Add fines.
2. Too dry granules. Moisten the granules properly and add proper amount
of binder.
3. Tablets expand. Improve granulation. Add dry binders.
4. Granulation too cold. Compress at room temperature.

The Causes and Remedies of cracking related to MACHINE (Dies, Punches and Tablet
Press)

Sr. No. CAUSES REMEDIES

1. Tablet expands on ejection due to air entrapment. Use tapered die.
2. Deep concavities cause cracking while Use special take-off.
removing tablets

Sticking / Filming
Sticking / filming: ‘Sticking’ refers to the tablet material adhering to the die wall.
Filming is a slow form of sticking and is largely due to excess moisture in the granulation.
Reason: Improperly dried or improperly lubricated granules.

The causes and remedies of sticking/ filming related to formulation (Granulation) are as
follows:
Sr. CAUSES REMEDIES
No.
1. Granules not dried properly. Dry the granules properly. Make moisture analysis to
determine limits.
2. Too little or improper Increase or change lubricant.
lubrication.
3. Too much binder Reduce the amount of binder or use a different type of
binder.
4. Hygroscopic granular Modify granulation and compress under controlled

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 material. humidity.
5. Oily or way materials Modify mixing process. Add an absorbent.
6. Too soft or weak granules. Optimize the amount of binder and granulation
technique.

The Causes and Remedies of sticking / filming related to MACHINE (Dies, Punches and
Tablet Press)
Sr. No. CAUSES REMEDIES
1. Concavity too deep for granulation. Reduce concavity to optimum.
2. Too little pressure. Increase pressure.
3. Compressing too fast. Reduce speed.

Picking

Picking: ‘Picking’ is the term used when a small amount of material from a tablet is sticking to
and being removed off from the tablet-surface by a punch face.
The problem is more prevalent on the upper punch faces than on the lower ones. The problem
worsens, if tablets are repeatedly manufactured in this station of tooling because of the more and
more material getting added to the already stuck material on the punch face.

Reason: Picking is of particular concern when punch tips have engraving or embossing letters,
as well as the granular material is improperly dried.

The causes and remedies picking related to formulation (Granulation) are as follows:
Sr. CAUSES REMEDIES
No.
1. Excessive moisture in granules. Dry properly the granules, determine
optimum limit.
2. Too little or improper lubrication. Increase lubrication; use colloidal silica as a
‘polishing agent’, so that material does not
cling to punch faces.
3. Low melting point substances, may Add high melting-point materials. Use high
soften from the heat of compression and meting point lubricants.
lead to picking.
4. Low melting point medicament in high Refrigerate granules and the entire tablet
concentration. press.
5. Too warm granules when compressing. Compress at room temperature. Cool
sufficiently before compression.
6. Too much amount of binder. Reduce the amount of binder, change the type
or use dry binders.

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The Causes and Remedies of picking related to MACHINE (Dies, Punches and Tablet
Press)
Sr. CAUSES REMEDIES
No.
1. Rough or scratched punch faces. Polish faces to high luster.
2. Embossing or engraving letters on punch Design lettering as large as possible.
faces such as B, A, O, R, P, Q, G. Plate the punch faces with chromium to
produce a smooth and non-adherent face.
3. Bevels or dividing lines too deep. Reduce depths and sharpness.
4. Pressure applied is not enough; too soft Increase pressure to optimum.
tablets.

Binding

Binding: ‘Binding’ in the die, is the term used when the tablets adhere, seize or tear in the die. A
film is formed in the die and ejection of tablet is hindered. With excessive binding, the tablet
sides are cracked and it may crumble apart.

Reason: Binding is usually due to excessive amount of moisture in granules, lack of lubrication
and/or use of worn dies.

The causes and remedies binding related to formulation (Granulation) are as follows:
Sr. CAUSES REMEDIES
No.
1. Too moist granules and extrudes Dry the granules properly.
around lower punch.
2. Insufficient or improper lubricant. Increase the amount of lubricant or use a more
effective lubricant.
3. Too coarse granules. Reduce granular size, add more fines, and
increase the quantity of lubricant.
4. Too hard granules for the lubricant Modify granulation. Reduce granular size.
to be effective.
5. Granular material very abrasive and If coarse granules, reduce its size.
cutting into dies. Use wear-resistant dies.
6. Granular material too warm, sticks Reduce temperature.
to the die. Increase clearance if it is extruding.

The Causes and Remedies of binding related to MACHINE (Dies, Punches and Tablet
Press)
Sr. CAUSES REMEDIES

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No.
1. Poorly finished dies. Polish the dies properly.
2. Rough dies due to abrasion, Investigate other steels or other materials or modify
corrosion. granulation.
3. Undersized dies. Too little Rework to proper size.
clearance. Increase clearance.
4. Too much pressure in the tablet Reduce pressure. OR
press. Modify granulation.

Mottling

Mottling: ‘Mottling’ is the term used to describe an unequal distribution of color on a tablet,
with light or dark spots standing out in an otherwise uniform surface.

Reason: One cause of mottling may be a colored drug, whose color differs from the color of
excipients used for granulation of a tablet.

The causes and remedies of mottling:

Sr. CAUSES REMEDIES

No.
1. A colored drug used along Use appropriate colorants.
with colorless or white-
colored excipients.
2. A dye migrates to the surface Change the solvent system,
of granulation while drying. Change the binder,
Reduce drying temperature and
Use a smaller particle size.
3. Improperly mixed dye, Mix properly and reduce size if it is of a larger size to
especially during ‘Direct prevent segregation.
Compression’.
4. Improper mixing of a colored Incorporate dry color additive during powder blending
binder solution. step, then add fine powdered adhesives such as acacia
and tragacanth and mix well and finally add granulating
liquid.

Double impression

Double impression: ‘Double Impression’ involves only those punches, which have a monogram
or other engraving on them.

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Reason: At the moment of compression, the tablet receives the imprint of the punch. Now, on
some machines, the lower punch freely drops and travels uncontrolled for a short distance before
riding up the ejection cam to push the tablet out of the die, now during this free travel, the punch
rotates and at this point, the punch may make a new impression on the bottom of the tablet,
resulting in ‘Double Impression’.
If the upper punch is uncontrolled, it can rotate during the short travel to the final compression
stage and create a double impression.

The causes and remedies of double impression:

Sr. CAUSE REMEDIES
No.
1. Free rotation of either upper punch -Use keying in tooling, i.e. inset a key alongside of
or lower punch during ejection of the punch, so that it fits the punch and prevents
a tablet. punch rotation.
-Newer presses have anti-turning devices, which
prevent punch rotation.

Tablet coating

Tablet coating: Tablet coating is one of the oldest pharmaceutical processes still is in existence.
Coating is a process by which an essentially dry, outer layer of coating material is applied to the
surface of a dosage form in order to confer specific benefits over uncoated variety.
Steps of coating:

Suspension making (for about 45-60 minutes)

Compressed tablets (core) in feeding pan

Pre-jag (warm up for about 30 minutes at 40° temperature)

Drying and spraying of coating materials

Cooling

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 Unloading of coated tablet
Objective of tablet coating:
 Mask the odor, taste or color of the drug.
 Provides physical and chemical protection for drug.
 Controls the release of drug from the tablet.
 Protects the drug from gastric environment of stomach in case of acid sensitive drug.
 Avoids chemical incompatibility.
 Improves pharmaceutical elegance by using colors and contrasting printing.

Equipments of coating

The equipments used for the tablet coating are:

1. Standard coating pan
2. Perforated coating pan
3. Fluidized bed coater

Types of tablet coating

The coating of tablets classified into three types:

1. Sugar coating
2. Film coating

Sugar coating

Sugar coating: To coat the tablet with sugar is called sugar coating. This involves several steps,
the duration of which ranges from few hours to few days. The quality of coating depends upon
the skill of the operator specially in ladling type of solution application. The sugar coating results
in elegant highly glossed finished tablets.
Description of tablets: Smooth, rounded and polished to a high gloss.
Process: Sugar coating involves following steps:
 Sealing: It prevents moisture penetration in to the tablet core.
 Seal coating agents - shellac, zein, Oleicacid, PG, PEG4000, alcohol, methylene
chloride.

 Sub-coating: Sub coating is applied :

 To form uniform edges,

155
  To build up the tablet size.
Sub coating increases the tablet weight from 50 to 100 percent.
Examples- Gelatin, sugarcane powder, corn syrup, syrup, distilled water, Gum acacia.
 Syruping (smoothing): The purpose of this step is to cover and fill the imperfection in the
tablet surface caused by sub-coating step.
 Coloring: It is done to achieve a pleasant appearance there are two groups of coloring
substance generally used-
– H2O soluble dyes.
– H2O insoluble dyes.
 Polishing: This is the final step, the tablets can be polished in standard coating pan or canvas
line polishing pan.
Problems of sugar coating:
 Chipping of coating
 Cracking of the coating
 Non-drying coating
 Twinning (or build up of multiples)
 Uneven color
 Blooming and sweating
 Marbling
Advantages of sugar coating:
 It prevents unpleasant odor ,
 Give sweet taste to tablet by masking bitter taste,
 Highly elegant and glossed tablets are obtained.

Film coating
Film Coating: To reduce sugar coating process time and to reduce the requirement for operator
skill, film coating was developed. Film coating is a technique in which a thin layer/coat of a
polymer is deposited over the tablets/particulate.
Reasons for film coating:
 To improve product appearance, to mask odor and taste and aid in swallowing.
 To aid identification and hence, decreases the risk of confusion especially when patients
have to take several preparations.
 To separate incompatible active ingredients present in a repeat.
 To protect the active ingredient against heat, light and moisture.
 To create modified relapse form.

156
Materials used in film coating
A typical film coating formulation is made up of
1. Polymer (film former)
2. Plasticizer
3. Coloring/opacifying agent
4. Solvent
5. Others (surfactants, flavors, sweetening agent, active ingredients and preservatives)

Polymer

The function of the polymer is to provide main structure and basic physical and chemical
properties to the coating. Polymer viscosity is very important especially in aqueous coating we
need to minimize the water concentration, it is to shorten the process time and to minimize
product exposure to the moisture (moisture sensitive product). But the coating composition with
viscosity above 500 cps are difficult to atomize and will not produce smooth product. Therefore
polymers with low viscosity are preferred.
Different uses of polymers:
Immediate release Enteric coating Sustained release
Hypromellose Hypromellose phthalate HPMC
Carboxymethyl cellulose Polyvinyl acetate phthalate Eudragit
Hydroxyethyl cellulose Cellulose acetate phthalate Ethylcellulose
Hydroxyethylmethyl Polymethacrylates
cellulose
Hydroxypropyl cellulose Shellac
Polyethylene glycol
Ethylcellose
Hydroxypropylmethyl
cellulose

Plasticizer

Plasticizers are additives that increase the plasticity or fluidity of a material. They are used to
control the film formation process of coatings based on physically drying film forming materials.
 It is used to modify the quality of the film.
 Plasticizing techniques involve internal plasticizers and external plasticizers.
 Internal plasticizers involves Chemical modification of the basic polymer that alters the
physical properties of the polymers.

157
  Chemical plasticizers Additives of the Coating solution to achieve the desire effect of
the film (flexibility ,tensile Strength, adhesive properties)
 Level of plasticizers ranges from 1-50% by weight of film former.
Examples
Castor oil,
Propylene glycol,
Glycerin,
Surfactants e.g. Polysorbate (tweens), sorbitan, esters (spans), organic acid
esters.

Solvent

It is used to dissolve or disperse the polymers and other additives and convey them to the
substrate surface.
The ideal requirements of the solvent are:
 It should either dissolve or disperse the polymer system.
 It should have no environmental impact.
 It should easily disperse other coating solution components in to the solvent system.
 It should have rapid drying rate (ability to coat 300kg load in 3-5 hours)
 It should be colorless, tasteless, odorless, inexpensive, nontoxic, inert and noninflammable
and
 It should have rapid drying Rate.
Examples-Water, Ethanol, Methanol, Isopropanol, Chloroform, Acetone, Methylene chloride,
Methylene ethyl ketone.

Colorants
 It is to provide the distinct color and elegance to the dosage form.
 To achieve the proper distribution of suspended colorants in the coating solutions
requires Use of fine powdered colorants (<10 microns).
 The concentration of colorants in the coating solution depends on the color shade, desired
the type of dye and the concentration of the opaquant extenders.
 For very light shade conc. Lt 0.01%.
 For dark shade Conc. Mt 2.0% is required.
 The most common colorants in use are certified by FOOD DRUG AND COSMETICS
(FD&C) or DRUG AND COSMETIC (D&C) Colorants.
 These are lakes and dyes.
 Lakes are derived from dyes by precipitating with carriers e.g., Alumina or talc.

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An ideal coating material should have the following properties:
 Solubility in solvent of choice for coating preparation.
 Solubility required for the intended use.
 Capacity to produce an elegant looking product.
 Stability in the presence of heat, light, moisture, air and substrate being coated.
 Odorless, colorless and tasteless.
 Compatibility with other ingredients.
 Nontoxic or no pharmacologic activity.
 Ease of application.
 Resistant to cracking.
 No bridging or filling formation.
 Ease of printing on high speed machines

Advantages of film coating:

 Film coating gives a tablet with less Weight and small size.
 The film formed is very thin.
 In film coating engravings are possible on tablet surface which are not possible in
sugar coating.

Types of film coating

1. Non-enteric film coating

2. Enteric film coating
1. Non-enteric film coating: Non-enteric film coating is like sugar coating but film coating
agents are used. It is used to overcome the disadvantages of sugar coating.
Non-enteric film coating agents:
 HPMC (Hydroxy propyl methyl cellulose)
 MHEC (Methyl hydroxyl ethyl cellulose)
 EC (Ethyl cellulose)
 HPC (Hydroxy propyl cellulose)
 Povidone
 Na-CMC
 PG
 Acrylate polymers

2. Enteric film coating: The technique involved in enteric coating is protection of the tablet
core from disintegration in the acidic environment of the stomach by employing pH sensitive
polymer, which swell or solubilize in response to an increase in pH to release the drug.

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Objective of enteric film coating:
 To protect acid labile drugs from gastric fluid e.g. enzymes and certain antibiotics.
 To prevent gastric distress or nausea e.g. sodium salicylate.
 To deliver drug to intestine for local action.
 To deliver drugs that are optimally absorbed in the small intestine.
 To provide a delayed release component for repeat action tablets.

Enteric film coating agents:

 CAP (Cellulose acetate phthalate)
 Acrylate polymers
 HPMCP ( Hydroxypropyl methyl cellulose phthalate)
 PVAP (Polyvinyl acetate phthalate)

Problems and remedies for tablet coating

Blistering

Definition: It is local detachment of film from the substrate forming blister.

Reason: Entrapment of gases in or underneath the film due to overheating either during spraying
or at the end of the coating run.
CAUSE REMEDY
Effect of temperature on the strength, elasticity and adhesion of the Use mild drying
film. condition.

Chipping

Definition: It is defect where the film becomes chipped and dented, usually at the edges of the
tablet.
Reason: Decrease in fluidizing air or speed of rotation of the drum in pan coating
CAUSE REMEDY
High degree of attrition associated with Increase hardness of the film by increasing the
the coating process. molecular weight grade of polymer.

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 Cratering

Definition: It is defect of film coating whereby volcanic-like craters appears exposing the tablet
surface.
Reason: The coating solution penetrates the surface of the tablet, often at the crown where the
surface is more porous, causing localized disintegration of the core and disruption of the coating.
Sr. CAUSES REMEDIES
No.
1. Inefficient drying. Use efficient and optimum drying conditions.

2. Higher rate of application of Increase viscosity of coating solution to decrease

coating solution. spray application rate.

Sticking and Picking

Definition: It is defect where isolated areas of film are pulled away from the surface when the
tablet sticks together or to the coating pan and then detached from one another or from the pan
and piece of film get remained to the pan or the other tablet exposing the core.
Reason: Conditions similar to cratering that produces an overly wet tablet bed where adjacent
tablets can stick together and then break apart.
Sr. CAUSE REMEDY
No.
1. Inefficient drying. Use optimum and efficient drying conditions or increase
the inlet air temperature.
2. Higher rate of application of Decrease the rater of application of coating solution by
coating solution increasing viscosity of coating solution.

Pitting

Definition: It is defect whereby pits occur in the surface of a tablet core without any visible
disruption of the film coating.
Reason: Temperature of the tablet core is greater than the melting point of the materials used in
the tablet formulation.
CAUSE REMEDY
Inappropriate drying Dispensing with preheating procedures at the initiation of coating and
(inlet air ) modifying the drying (inlet air) temperature such that the temperature of
temperature the tablet core is not greater than the melting point of the batch of
additives used.

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 Blooming/Hazing/Dull Film

Definition: It is defect where coating becomes dull immediately or after prolonged storage at
high temperatures.
Reason: It is due to collection on the surface of low molecular weight ingredients included in the
coating formulation. In most circumstances the ingredient will be plasticizer.
CAUSE REMEDY
High concentration and low molecular Decrease plasticizer concentration and increase
weight of plasticizer. molecular weight of plasticizer.

Blushing

Definition: It is defect best described as whitish specks or haziness in the film.

Reason: It is thought to be due to precipitated polymer exacerbated by the use of high coating
temperature at or above the thermal gelation temperature of the polymers.
Sr. CAUSES REMEDIES
No.
1. High coating temperature Decrease the drying air temperature
2. Use of sorbitol in formulation which causes largest Avoid use of sorbitol with Hydroxy
fall in the thermal gelation temperature of the Propyl Cellulose, Hydroxy Propyl
Hydroxy Propyl Cellulose, Hydroxy Propyl Methyl Cellulose, Methyl Cellulose
Methyl Cellulose, Methyl Cellulose and Cellulose and Cellulose ethers.
ethers.

Color variation

Definition: A defect which involves variation in color of the film.

Reason: Alteration of the frequency and duration of appearance of tablets in the spray zone or
the size/shape of the spray zone.
CAUSE REMEDY
Improper mixing, uneven spray pattern, Go for geometric mixing, reformulation
insufficient coating, migration of soluble dyes- with different plasticizers and additives or
plasticizers and other additives during drying. use mild drying conditions.

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 Orange peel/Roughness

Definition: It is surface defect resulting in the film being rough and nonglossy. Appearance is
similar to that of an orange.
Reason: Inadequate spreading of the coating solution before drying.
Sr. No. CAUSES REMEDIES
1. Rapid Drying Use mild drying conditions
2. High solution viscosity Use additional solvents to decrease viscosity of solution.

Cracking/Splitting

Definition: It is defect in which the film either cracks across the crown of the tablet (cracking) or
splits around the edges of the tablet (Splitting)
Reason: Internal stress in the film exceeds tensile strength of the film.
CAUSE REMEDY
Use of higher molecular weight Use lower molecular weight polymers or polymeric
polymers or polymeric blends. blends. Also adjust plasticizer type and concentration.

Bridging and Filling

Definition: Films pulls out of intagliation forming bridge across the edges of the mark a blister.
CAUSE REMEDY

High internal stresses in film Increase the plasticizer content or changing

plasticizer

Capsule
Capsule: The word capsule is derived from the Latin “Capsula” meaning a small box. In
pharmacy, the word Capsules are solid dosage forms in which drug substance is enclosed within
hard or soft soluble shell. The shells are generally formed from gelatin.
Advantages of capsule:
 Capsules are tasteless, odorless and can easily be administered.
 Combination of powders we can use.
 They are attractive in appearance.
 The drugs having un-pleasant odor and taste are enclosed in a tasteless shell.
 They can be filled quickly and conveniently.
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 Physician can change the dose and combination of drug according to patient requirement.
 They are economical.
 They are easy to handle and carry.
Disadvantages of capsule:
 Production cost is higher.
 Hygroscopic drugs are not suitable for filling into capsules, because they absorb water
present in capsule shell makes shell very brittle and ultimately lead to crumble into pieces.
 The concentrated solutions which require previous dilution are unsuitable for capsules
because if administered as such lead to irritation into stomach.

Capsule size

Empty capsules ranging in size from 000 the largest to 5 the smallest. Generally, hard gelatin
capsule are used to encapsulate between 65 mg to 1 gram.
Size Volume in ml Size in mm
000 1.37 26.3
00 0.95 23.3
0 0.68 21.8
1 0.50 19.2
2 0.37 18.3
3 0.30 15.3
4 0.21 14.7
5 0.15 11.9

Figure: Different sizes of capsule

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 Gelatin

Gelatin: Gelatin is a mixture of peptides and proteins produced by partial hydrolysis of collagen
extracted from the skin bones and connective tissues of animals such as domesticated cattle
chicken, pigs.
Types of gelatin:
There are two basic types of gelatin:
TYPE A: Derived from acid treated precursor that exhibits an iso electric point at pH-9. It is
manufactured mainly from pork skin.
TYPE B: Derived from alkali treated precursor that exhibits an iso electric point at pH-4.7. It is
manufactured mainly from animal bones.
Preparation of Gelatin:
Dry bone Calf skin Pork skin
Bone meal
5% HCl,10-15 days wash wash
Dicalcium
Phosphate Lime 10%, 6-12wks Acid 1-5% HCl 10-30 hrs

Lime 10%, 4-8% wks

pH adjustment Water-wash 10-30hrs Acid removed

Hot water extraction

Filter
Vacuum concentration
Cool to solidify
Air dry
Mill to size

Figure: Flow chart for gelatin production process.

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 Types of capsules

Capsules are of two types:

1. Hard gelatin capsules
2. Soft gelatin capsules
1. Hard gelatin capsules: A hard gelatin capsule is a type of capsule that is usually used to
contain medicine in the form of dry powder or very small pellets. Hard gelatin capsules are
usually filled with powders, granules, tiny pellets.
Advantages and disadvantages of hard gelatin capsules:

Advantages: Disadvantages
 Rapid drug release.  Filling equipment is slower.
 Come in different shapes and  Stick together.
sizes.  Made out of the bones and skins of
 Good oxygen barriers. pigs.

2. Soft gelatin capsules: Soft Gelatin capsules are one piece, hermetically sealed, containing a
liquid, a suspension, or a semisolid. Soft gelatin is mainly composed of gelatin, plasticizers,
preservative, colouring and opacifying agents, flavoring agents and sugars.
Advantages and disadvantages of soft gelatin capsules:

Advantages: Disadvantages:
 Easy to swallow.  Stick together.
 Taken in various ways such as oral,  Costly.
topical, and chewable.  Made out of the bones and skins of
 Tamper-resistant. pigs.

Difference between Hard and Soft Gelatin Capsule:

Hard gelatin capsule Soft gelatin capsule
Two piece (large body & short cap) One piece & hermetically sealed.

Cylindrical shape. Available in round, oval & tube like shapes.

Powder drug or pellets coated with drug are Liquid & Semi liquid fill & unstable
encapsulated substances are encapsulated.

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Gelatin in Hard form is used. Molten gelatin are used.

Capsules are sealed after they are filled to Filling & sealing of soft gelatin capsules are
ensure that the medicaments may not come done in a combined operation on machine.
out of the capsule due to rough handling.

8 different type of sizes are available No specific sizes are available.

Microencapsulation

Microencapsulation: Microencapsulation is a process by which solids, liquids or even gases

may be enclosed in microscopic particles by formation of thin coatings of wall material around
the substances. Particles having diameter between 3 - 800µm are known as micro particles or
microcapsules or microspheres. Particles larger than 1000µm are known as Macro particles.
Objective of microencapsulation:
 For sustained or prolonged drug release.
 For masking taste and odor of many drugs to improve patient compliance.
 For converting liquid drugs in a free flowing powder.
 To reduce toxicity and GI irritation.
 Incompatibility among the drugs can be prevented by microencapsulation.
 The drugs, which are sensitive to oxygen, moisture or light, can be stabilized by
microencapsulation.
Application of microencapsulation:
 To improve the flow properties. e.g. Thiamine, Riboflavine
 To enhance the stability. e.g. Vitamins
 To reduce the volatility of materials. e.g. Peppermint oil, Methyl salicylate
 To avoid incompatibilities. e.g. Aspirin and Chloramphenicol
 To mask the unpleasant taste and odor. e.g. Aminophylline, castor oil
 To convert liquids into solids. e.g. Castor oil, Eprazinone,
 To reduce gastric irritation. e.g. Nitrofurantoin, Indomethacin
Advantages of microcapsules:
 To Increase of bioavailability.
 To alter the drug release.
 To improve the patient’s compliance.
 To produce a targeted drug delivery.
 To reduce the reactivity of the core in relation to the outside environment.
 To decrease evaporation rate of the core material.
 To convert liquid to solid form & to mask the core taste.
Disadvantages of microcapsules:

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  Organic solvents are used in this process, which is very much toxic to the body.
 It can easily be spoiled in the autoclave.
 Coagulation of drugs can easily be occurred.

Liquid dosage forms

Liquid dosage forms: Liquid dosage forms are essentially pharmaceutical products in the form
which involves a mixture of active drug components and nondrug components (excipients).
Liquid form of a dose of a drug used as a drug or medication intended for administration or
consumption. Liquid dosage forms are prepared: a. By dissolving the active drug substance in an
aqueous or non-aqueous (e.g. alcohol, ether, glycerin) solvent, b. By suspending the drug in
appropriate medium, or c. By incorporating the drug substance into an oil or water phases.

Liquid

Monophasic Biphasic

Liquids meant for internal Liquids meant for external

administration
administration

Syrups
Elixirs
Liquids applied Liquids used in Liquids instilled
Linctuses into body cavities
to the skin mouth
Mixtures
Lotions Gargles Douches
Liniments Mouthwashes Ear drops
Collodions Throat paints Nasal drops
Paints Eye drops
Enemas

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 Biphasic

Liquid in liquid Solid in liquid

Oral use External use

Parenteral Opthalmic Oral use External

l
Suspension, Emulsion Lotion
Diffusible, Indiffusible
Figure: Pharmaceutical liquid dosage form
Advantages of liquid dosage form:
 Better for patients who have trouble in swallowing solid dosage form.
 Faster absorption than solids.
 More flexibility in achieving the proper dosage of medication.
 Palatable.
 Best choice for children and old age person.
Disadvantages of liquid dosage form:
 Shorter life than other dosage form.
 Harder to measure accuracy.
 Need special storage condition.
 Less stable.
 Easily affected by microorganisms.
 Bulky to carry around.
 Easy to loss by the breakage of the container.

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  Measuring dose is required.

Administration of liquid dosage form:

Liquid dosage forms can be administered:
 Topically - lotions or suspension applied to the skin, nasal drops, ear drops, eye solutions.
 Orally (p.o.) – oral suspension, emulsion & solution.
 Parenterally -
 Subcutaneous injection (s.c.).
 Intramuscular injection (i.m.).
 Intravenous administration (i.v.).
Classification of liquid dosage form:
Liquid dosage forms commonly encountered in pharmaceutical practice are either monophasic or
biphasic.
Monophasic systems are characterizes by the presence of a single homogeneous phase e.g.
solution, mixtures, ear drops, nasal drops, etc. whereas biphasic liquid dosage forms consists of
two distinct phases e.g. emulsions and suspensions.
Liquid preparations may be classified two categories:
1. Internal liquid preparations:
 Monophasic liquid preparations include- Syrups, Solution, Elixir and Linctuses.
 Biphasic liquid preparations include- emulsions and suspensions.
2. External liquid preparations:
 Applied on the skin. This includes- Lotions, Liniments, Collodions, Throat paints.
 Instilled into body cavities. This include- Douches, Ear drops, Nasal drops, Eye drops,
Enemas.
 Used in the mouth. This includes- Gargles, Mouthwashs.

Pharmaceutical solutions
Solutions: Solutions are one of the oldest dosage forms used in the treatment of patient and
afford rapid and high absorption of soluble medicinal products. Solutions are evenly distributed,
homogenous mixtures of dissolved medication in a liquid vehicle. Molecules of a solid, liquid, or
gaseous medication are equally distributed among the molecules of the liquid vehicle. Because
the medication is already dissolved in the solution, it is absorbed from the stomach, skin, or other
site of administration more quickly than other medication dosage forms.
Solution = Solvent + Solute
Solvent: An agent which can dissolve one or more substance to form a solution.

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Solute: The substance which is dissolved by the solvent.

Classification of solution:
1. According to the route of administration-
 Oral solutions: Through oral route.
 Otic solutions: Installed in the ears.
 Ophthalmic Solution: installed in the eyes.
 Topical solutions: Applied over the surface.

2. According to composition and uses:

 Syrup: Aqueous solution containing sugar.
 Elixir: Sweetened hydroalcoholic (combination of water and ethanol) solution.
 Spirit: Solution aromatic materials in alcohol.
 Aromatic water: Solution of aromatic material in water.
 Tincture/ Fluid extract: Solution prepared by extracting active constituents from crude
drugs. E.g. compound cardamom tincture. They may also be solutions of chemical
substances dissolved in alcohol or hydroalcoholic solvent. E.g. Tincture of Iodine.
 Injection: Certain solution prepared to be sterile and pyrogen-free and intended for
parenteral administration.
Classification of solutions based on characteristics of the vehicle:
A. Aqueous and viscous aqueous solutions: Aqueous and viscous aqueous solutions use
purified water as the vehicle. Aqueous solutions may be ingested orally, applied topically, or
injected into the bloodstream. Viscous aqueous solutions are sticky, thick, sweet solutions
that are either liquid or semisolid. Syrup is example of viscous aqueous solutions.
B. Non-aqueous solutions: Non-aqueous solutions are those that utilize solvents, or dissolving
liquids, in addition to or instead of water. Commonly used non-aqueous solvents include
alcohol (ethyl alcohol or ethanol), glycerin, and propylene glycol. Non-aqueous solutions that
employ alcohol and their solvent are call alcoholic solutions.
C. Hydro alcoholic solutions: Hydro alcoholic solutions are solutions those contain alcohol in
addition to water. Elixir and spirits are example of hydro alcoholic solutions.
Classification solutions based on their physical appearance:
A. Saturated solution: A solution containing maximum amount of solutes, dissolve in it.
B. Unsaturated solution: A solution in which the solvent is capable of dissolving more solutes
at a definite temperature.
C. Supersaturated solution: A solution where saturation point has been reached, but contains
more solutes due to heating.
Classification of solutions based on their permeability through cell membrane:

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1. Colloidal solution: A solution in which the solute particles cannot pass through the semi-
permeable membrane. (Colloidal particles: particles ranging from 1 nm-200nm). E.g.
Albumin solution
2. Crystalloidal solution: A solution where the solute particles can pass through the semi-
permeable membrane. E.g. sugar solution.
Classification of solutions based on the expression of concentration:
1. Percent solution:

a. Percent by weight (w/w): This indicates the number of grams of solute per 100-gram
solution. E.g. 10% Dextrose (w/w) means 10gm Dextrose in 100gm solution.

b. Percent by volume (w/v): This indicates the number of grams of solute per 100 ml solution.
E.g. 5% NaCl (w/v) means 5gm NaCl in 100 ml solution.

c. Percent by volume (v/v): This indicates the number milliliters of solute per 100 ml of
solution. E.g. 5% Alcohol (v/v) means 5 ml alcohol in 100 ml solution.

2. Molar solution:
When a solution contains 1gm molecular weight of solute per liter of solution, then it is called 1
molar or 1M solution. E.g. 1gm molecular weight of HCl = 36.5gm HCl. So, 1 molar solution of
HCl contains 36.5gm HCl/liter of solution.
3. Molal solution:
When a solution contains 1gm molecular weight of solute per kg of solvent, then it is called 1
molal or 1m solution. E.g 1 molal solution of HCl contains 36.5gm HCl/kg of solvent.
4. Normal solution:
When a solution contains 1gm equivalent weight of solute per liter of solution, then it is called 1
normal or 1 N solution. E.g. 1gm equivalent weight of H2SO4 is 49 gm. so, 1N solution of H2SO4
= 49gm so, 1N solution of H2SO4 contains 49gm H2SO4 / liter of solution.
5. Osmolar solution:
When a solution contains 1 osmole solute per liter of solution, then it is called osmolar solution.
E.g. 1 osmole of NaOH= 20 gm.
So, 1 osmolar solution of NaOH contains 20 gm NaOH/liter of solution.
6. Osmolal solution:
When a solution contains 1 osmole solute per kg of solvent, then it is called 1 osmolal solution.
E.g. 1 osmolal solution of NaOH contains 20 gm NaOH / kg of solvent.

172
Classification of solutions based on the tonicity:
1. Isotonic solution: A solution that has an osmotic pressure equal to that of plasma osmotic
pressure is called isotonic solution. E.g. 0.9% NaCl, 5% Dextrose.

2. Hypertonic solution: A solution that has an osmotic pressure greater than that of plasma
osmotic pressure is called hypertonic solution. E.g. 10% Dextrose, 20% Mannitol.

3. Hypotonic solution: A solution that has an osmotic pressure lower than that of plasma
osmotic pressure is called hypotonic solution. E.g. 0.45% NaCl.

Osmole, Osmolality, Osmolarity, Diffusion, Osmosis, Osmotic pressure

Osmole: It is the standard unit of osmotic pressure. Osmole is equal to the gram molecular
weight of a substance divided by the number of ions into which it dissociates in solution.
e.g. Gram molecular weight of NaCl is 58.5 gm. NaCl dissociates into ions in solution (Na +, Cl-)
so, 1 osmole (osm) of NaCl = 58.5/2= 29.52gm so, if a solution contains 58.5gm NaCl in 1000
ml, then it will be 2 osmolar solutions.
Osmolality: Number of osmoles of solute per kg of solvent.
Osmolarity: Number of osmoles of solute per liter of solution. E.g. Osmolarity of plasma is 290
miliOsm/L (Range: 275-300 mOsm/L.).
Diffusion: Diffusion is a process in which solute particles move from higher concentration to
lower concentration. E.g. The movement of O2 across the alveolar memebrane in the lungs.
Osmosis: Migration of solvent from the solution of lower concentration to the higher
concentration, when they are separated by a semi-permeable membrane is called osmosis.
The rate of osmosis depends on-
 The concentration of solutes in the solution.
 The temperature of the solution.
 The electrical charges of solution.
 The difference between the osmotic pressure exerted by the solution.
Osmotic pressure: It is pressure necessary to prevent solvent migration through semi-permeable
membrane. It depends upon the number of particles per unit volume of the solvent.
Q: why 5% Dextrose is isotonic?
5% Dextrose solution means→
100 ml solution contains 5gm Dextrose
∴ 1 ml solution contains 5/100 gm Dextrose

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∴ 1000 ml solution contains 5×1000/100gm Dextrose or, 50gm Dextrose.
Now, as dextrose (C6H12O6) does not dissociate into any ions in solutions, so it has the same
number of moles or osmoles in a definite amount.
∴ 1 mole or 1 osmole of dextrose= 180 gm Dextrose.
So, 180gm dextrose = 1 osmole
∴ 1 gm dextrose = 1/180 osmole
∴ 50 gm dextrose = 50/180 osmole
= 0.2777osmole
=277.7 mOsm.
∴ 5% dextrose solution has an Osmolarity of 277.7 mOsm/L.
Since its Osmolarity is close or approximate to that of blood, thus it is considered as isotonic.

Solubility

When a solid solute is dissolved in a liquid solvent two types of interactions are evident one is
the intra-molecular force between the solute molecules and the other is the intramolecular force
between the solute and solvent molecules. When a solute dissolves, the substance’s intra-
molecular forces (cohesive force) must be overcome by the force of attraction between the solute
and solvent molecules (adhesive force). This involves breaking the solute- solute forces and the
solvent- solvent forces to achieve the solute- solvent forces attraction.
Some important definition and terms:
Acidifying agents: The materials used in liquid preparation to provide acidic medium for
product stability. Ex: Citric acid, Acetic acid, HCl.
Alkalinizing agent: The materials used in liquid preparation to provide alkaline medium for
product stability. E.g. Sodium carbonate, Sodium hydroxide, Potassium hydroxide.
Adsorbent: An agent capable of holding other molecules onto its surface by physical or
chemical means. E.g. Activated charcoal, Powdered cellulose.
Antifungal preservatives: An agent used in liquid and semisolid preparations to prevent the
growth of fungi. E.g. Ethyl paraben, Methyl paraben, Benzoic acid, Sodium benzoate.
Antimicrobial preservative: An agent used in liquid and semisolid preparations to prevent the
growth of microorganism. E.g. Phenol, Phenyl ethyl alcohol, Formaldehyde.
Anti-oxidant: An agent that inhibits oxidation and thus is used to prevent the deterioration of
preparations. E.g. Ascorbic acid, Tocopherol, Sodium thiosulfate.

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Buffering agent: An agent used to resist change in pH upon dilution or addition of acid or alkali.
E.g. Potassium phosphate, Sodium acetate.
Chelating agent: An agent that forms stable, water soluble complex (chelates) with metals. E.g.
Edetic acid, Edetate sodium.
Surfactant: An agent used to reduce interfacial tension. May be used as wetting agents,
detergents or emulsifying agents. E.g. Polysorbate 80, Sodium lauryl sulfate.
Encapsulating agent: Agent used to form thin shells for the purpose of enclosing a drug
substance or drug formulation for ease of administration. E.g. Gelatin. Cellulose Acelate
Phthalate (CAP).
Suspending agent: An agent used in suspension to increase the viscosity of the continuous
phase so that the particles remain suspended for a sufficient long time. E.g. Methylcellulose,
Carboxymethylcellulose. Sodium carboxymethylcellulose.
Sweetening agent: An agent used to impart sweetness to a preparation. E.g. Saccharin, Lactose,
Glycerin, Sorbitol, Mannitol.
Flavorant: An agent used to impart a pleasant flavor and often odor to a pharmaceutical
preparation. E.g. Peppermint oil, Menthol, Vanillin, Orange oil.
Viscosity increasing agent: An agent used to change the consistency of a preparation to render
it more resistant to flow. E.g. Tragacanth, Sodium alginate, Acacia, Povidone.
Colorant: An agent used to impart color to liquid and solid pharmaceutical preparations. E.g.
FD and Red No. 3, FD and C yellow No.6, Caramel.
Tonic agents: Glycerin, Dextrose, NaCl, KCl.

Pharmaceutical suspension

These are mainly of 2 types: 1. Suspensions 2. Emulsions

Suspensions: A Pharmaceutical suspension is a coarse dispersion in which internal phase
(therapeutically active ingredient) is dispersed uniformly throughout the external phase.
Internal Phase:
This phase consisting of insoluble solid particles having a range of size ( 0.5 to 5 microns) which
is maintained uniformly throughout the suspending vehicle with the aid of suspending agents.
External Phase:
This phase is aqueous in some instances, may be an organic or oily liquid for nonoral use.
Reasons for the formulation of a suspension:

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  When the drug is insoluble in the delivery vehicle.
 To mask the bitter taste of the drug.
 To increase drug stability.
 To achieve sustained drug release.

Classification of suspension

1. On Basis of Route of Administration:

 Oral Suspensions. E.g. Parcetamol suspension

 Topical suspensions. E.g. Calamine Lotion
 Parentral suspensions. E.g. Insulin Zinc suspension

2. Based on proportion of Solid Particles:

 Dilute suspension: Concentration ranges from 2 to 10% w/v solid. E.g. Cortisone
acetate, Predinisolone acetate.
 Concentrated suspension: Concentration ranges from 50%w/v solid E.g. Zinc oxide
suspension.

3. Based on Size of Solid Particles:

 Colloidal suspension:
Suspensions having dispersed particle size less than 1 micron. It can be seen by electron
microscope.
 Coarse suspension:
Suspension having particle size of greater than 1 micron, can be seen by microscope.
 Nano suspension (10 ng):
Suspension having Nano sized drug particles i.e. less than 1mm.
Advantages of suspension:
 Can improve chemical stability of certain drugs.
 Duration and onset of action can be controlled. E.g. Protamine Zinc-Insulin suspension
 Suspension can mask the unpleasant/ bitter taste of drug. E.g. Chloramphenicol
 Higher rate of bioavailability, as order of bioavailability is:
Solution > Suspensions > Capsules > Compressed tablets
Disadvantages of suspension:
 Physical stability, sedimentation and compaction can cause problems.
 It is bulky sufficient care must be taken during handling and transport.
 It is difficult to formulate.

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  Uniform and accurate dose cannot be achieved unless suspension are packed in
unit dosage form.
Pharmaceutical applications of suspension:
 For delivery of poor soluble drugs. E.g. Prednisolone suspension.
 To improve stability of drug. E.g. Oxytetracycline suspension.
 To mask the unpleasant taste. E.g. Chloramphenicol palmitate suspension.
 Can be formulated for topical use. E.g. Calamine lotion.
 Vaccines are often formulated. E.g. Cholera vaccine.
 X-ray contrast agent are also formulated as suspension. E.g. Barium sulphate for
examination of alimentary tract.

Flocculation and Deflocculation

Flocculated suspensions: Flocs (loose aggregates) are first formed, increasing the
sedimentation rate due to increase in size of sedimenting particles. Hence, flocculated
suspensions sediment more rapidly. Sedimentation depends not only on the size of the flocs but
also on the porosity of flocs (liquid entrapped).
Deflocculated suspensions: Individual particles are settling, so rate of sedimentation is slow
which prevents entrapping of liquid medium which makes it difficult to re-disperse by agitation.
This phenomenon also called 'cracking' or 'claying.

Differences between flocculated and deflocculated suspensions:

Flocculated suspensions Deflocculated suspensions
In this system solids aggregate by forming In this system solids as present as individual
chemical bridges. particles. They also exhibit aggregation but
comparatively low than flocculated.
Un slightly sediment and supernatant layer is Pleasant appearance because of uniform
formed. dispersion of particles.
Particles exhibit attractive forces Particles exhibit repulsive forces
They settle as flocs Particles settle independently
Rate is high as flocs are collection of smaller Rate of sedimentation is slow and size of
particles particle is small.
Particles form loose aggregates Particles exist as separate entities

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Bioavailability is comparatively less. Bioavailability is relatively high.

Flock
Cake

Pharmaceutical emulsion

Pharmaceutical emulsion: An emulsion is a thermodynamically unstable system consisting of

at least two immiscible liquid phases one of which is dispersed as globules in the other liquid
phase stabilized by a third substance called emulsifying agent.
Types of pharmaceutical emulsion:
Simple emulsions (Macro emulsions):
 Oil-in-water (O/W)
 Water-in-oil (W/O)
Multiple emulsions:
 Oil-in-water-in-oil (O/W/O)
 Water-in-oil-in-water (W/O/W)
Micro emulsions: These are clear transparent solutions particle size ranges from 10-200nm.

Advantages of emulsions:

 Unpalatable oils can be administered in palatable form.

 Unpalatable oil-soluble drugs can be administered in palatable form.
 The aqueous phase is easily flavoured.
 The oily sensation is easily removed.
 The rate of absorption is increased.
 It is possible to include two incompatible ingredients, one in each phase of the emulsion.

Disadvantages of emulsions:

 Preparation needs to be shaken well before use.

 A measuring device is needed for administration.
 A degree of technical accuracy is needed to measure a dose.
 Storage conditions may affect stability.
 Bulky, difficult to transport and prone to container breakages.
 Liable to microbial contamination which can lead to cracking.

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Differences between emulsions and suspensions:
Emulsions Suspensions
These are biphasic liquid preparations These are biphasic liquid dosage form of
containing two immiscible liquids one of medicament in which finely divided solid
which is dispersed as minute globules into the particles are dispersed in a liquid
other
Globule size of the dispersed liquid is in the Particle size of suspended solid is in the range
range of 0.25 to 25µm of 0.5 to 5 microns
Emulsifying agent is required to make a stable Suspending agent is required to make a stable
emulsion suspension

Suspending agent is required to make a stable Suspensions are of two types flocculated and
suspension Emulsions are of two types oil-in- deflocculated
water type and water-in-oil type
There are several tests to confirm type of There are no tests to confirm type of
emulsion suspension
During storage freezing should be avoided as During storage freezing should be avoided as
it may lead to cracking it leads to aggregation

HLB value

HLB (Hydrophilic-Lipophilic Balance) value: The hydrophilic-lipophilic balance of a

surfactant is a measure of the degree to which it is hydrophilic or lipophilic, determined by
calculating values for the different regions of the molecule, as described by Griffin in 1949 and
1954.
Relation between HLB range and surfactant application:
Sl No. HLB range Use
1 0-3 Antifoaming agents
2 4-6 W/O emulsifying agents
3 7-9 Wetting agents
4 8-18 O/W emulsifying agents
5 13-15 Detergents
6 10-18 Solubilizing agents

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 Semi solid preparation

Semi solid: Semi solid pharmaceutical system comprise a body of product, which when applied
to skin or accessible mucous membranes tends to alleviate or treat a pathological condition or
other protection against harmful environment.
Examples of semi-solids: Creams, ointments, gels, pastes, and poultices.
Ideal properties of Semi solid dosage form:
 Smooth texture
 Elegant in appearance
 Non dehydrating
 Non gritty
 Non greasy and non staining
 Non hygroscopic
 Non irritating
 Do not alter membrane function
 Miscible with skin secretion

Types of semi-solids

Ointments: Ointments are homogenous, translucent, viscous, semi-solid preparation intended

for external application to skin or mucous membranes. Ointment may be medicated or not.
Uses:
 Emollient
 Application for active ingredients to the skin
Creams: Viscous semi solid emulsion with opaque appearance as Contrasted with translucent
ointments. Consistency depends on whether the cream is W/O or O/W.
Pastes: Contains high percentage of insoluble solid (usually 50% or more). Pastes are usually
prepared by incorporating solids directly into a congealed system by levigation with a
portion of base to form paste like mass. They have good adhesion on skin and less greasy.
Poultices: They are solid masses of solid matter applied to skin in order to reduce inflammation
and in some cases to act as a counter irritant. Poultices must retain heat for a considerable time.
After heating the preparation is spread on dressing and applied to the affected area. E.g: Kaolin
poultice (B.P.C).
Gels and Jellies: Gels are semi solid system in which liquid phase is constrained. With a 3-d
polymeric matrix having a high degree of physical or chemical cross linking. Gels are aqueous
colloidal system of hydrated forms of insoluble medicaments.

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Jellies are transparent or translucent non greasy semisolid and contain more water than gels.
Used for medication, lubrication and carrier for spermicidal agents to be used intra vaginally
with diaphragm.
Lotion: Lotions are similar to solutions but are thicker and tend to be more emollient in nature
than solution. They are usually oil mixed with water and more often than not have less alcohol
than solutions.
Gullies: These are transparent or translucent non greasy semisolid gel. Here the coherent matrix
is rich in liquid.
Liniment: Liniment is a medicated topical preparation for application to the skin. Sometimes
called balms, liniments are of a similar or lesser viscosity than lotions and are rubber in to create
friction, unlike lotions, ointments or creams.
Difference between ointment and cream:
Ointment Cream
Ointments are hydrocarbon semisolid base Creams are viscous semisolid preparation it
preparation but not viscous. may be w/o or o/w types.
Ointments are not easily removal. Due to the presence of water soluble base,
creams are easily removal.
Ointments have relatively higher body Creams have lighter body than ointments.
creams.
Monophase preparation. Multiphase preparation.

Difference between jellies and paste:

Jellies Pastes
Jellies are transparent or translucent and non- Pastes are not transparent or translucent and
greasy. less-greasy.
Do not contain finely powdered medicaments. Contain a high proportion of finely powdered
medicament.
Have pleasant cooling effect. Have no cooling effect.
Contain gelatin or carbohydrate. Do not contain gelatin or carbohydrate.
May also be used as lubricant. Do not used as lubricant.
Can be applied to the hairy parts of the body. Generally Cannot be applied to the hairy parts
of the body.

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 Preservatives

Preservatives: A bacteriostatic or bacteriocidal agent added to some multiple doses parenterals

and most cosmetics. E.g. Benzalkonium chloride (BAC), Formaldehyde and thimerosal
(merthiolate).
Product Preservative Concentration % of USP
type (%W/V) formulations in
which preservatives
used
Parenteral Benzyl alcohol 0.1-3.00 31.0
Methyl/Propyl paraben 0.08-0.01/ 13.8
0.001-0.023
Phenol 0.2-0.5 7.9
Methyl paraben (alone) 0.1 6.6
Chlorbutanol 0.25-0.5 5.3
Sodium 0.025-0.66 5.3
metabisulphite
0.13-0.2 2.6
Sodium bisulphite

Opthalmic Benzalkonium chloride 0.0025-0.133 50.0

Thiomersal 0.001-0.5 19.8
Methyl/Propyl paraben 0.05/0.01 6.6
Benzalkonium 0.01/0.1 3.3
Chloride plus EDTA
Oral Sodium benzoate NA 34.4
Methyl/Propyl Paraben NA 18.8
Methyl paraben (alone) 0.1 9.7
Methyl paraben Plus NA 7.5
Sodium benzoate
Creams Benzyl alcohol 1.0-2.0 25.4
Methyl/paraben NA 18.6

Methyl paraben (alone) 0.1-0.3 11.9

Benzoic acid 0.2 8.5
Sorbic acid 0.1 8.5
Chlorocresol 0.05 6.8

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 Aerosol preparation

Aerosol or Pressurized package is defined as “A system that depends on the power of a

compressed gas or liquefied gas to expel the contents from the container.”
Pharmaceutical Aerosol is defined as aerosol product containing active ingredients dissolved,
suspended or emulsified in a propellant or a mixture of solvent and propellant and intended for
oral or topical administration or for administration into the eye, nose, ear, rectum and vagina.
In 1942 - First aerosol was developed (insecticide).
In1950 - Pharmaceutical aerosol for topical administration was developed.
In 1955 - Aerosol for the local activity in the respiratory tract was developed (Epinephrine).

Advantages of aerosol:
 A dose can be removed without contamination of materials.
 Stability is enhanced for these substances adversely affected by oxygen and or moisture.
 When sterility is an important factor, it can be maintained while a dose is being
dispensed.
 The medication can be delivered directly to the affected area in a desired form.
(Localized action)
 Irritation produced by the mechanical application of topical medication is reduced or
eliminated.
 Ease and convenience of application.
 Application of medication in thin layer.
 Rapid response to the medicament.
 Bypasses first pass effect.
Disadvantages of aerosol:
 Limited safety hazard (Flammable Nature)
 It is a costly preparation
 Expensive Catalytic oxidation of drugs. e.g. Ascorbic acid and Epinephrine
 It is a chance for continuous deposition of particle in upper respiratory tract
 The propellant may cause chillness to the skin, Discomfort on injured skin
 Chlorofluorocarbon propellants cause Ozone layer depletion
Components of aerosol:
Propellant: Responsible for developing proper pressure within the container. Provide driving
force to expel the product from the container.
Container: They must be able to withstand pressures as high as 140 to 180 psig (pounds per sq.
inch gauge) at 130 ° F.
Valve and actuator: Capable of delivering the content in the desired form such as spray, foam,
solid stream etc.

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Product concentrate: Active ingredient or mixture of active ingredients and other necessary
agents such as solvents, anti-oxidants and surfactants.
Types of aerosol spray:
There are four types of Aerosol Sprays:
1. Space sprays:
 Its products are delivered in a fine mist.
 It contains 85% propellant and it is pressurized at 30-40psi and 70 °F.
 It contains not more than 50µm of particle. So it can be retaining in air.
 E.g. Room Sprays, Insecticidal spray.
2. Surface coating spray:
 Aerosols intended for carrying active ingredients to surface are termed as surface sprays
or surface coating spray.
 It contains 30 –70% propellant operates between 22–55 psig at 70F.
 E.g. Hair spray, Paint spray.
3. Foam spray:
 Foam aerosols (emulsion) usually operate between 35 and 55 psi at21°c and contains
only 6-10% propellant.
 E.g. Saving cream, sunburn preparation, shampoo, vaginal contraceptive foam aerosol.

4. Stream aerosol: Product expelled from the container without any gas from the aerosol.
Examples: Liquid shampoo, Vitamin shampoo, hand lotion, cough syrup.

Metered- Dose Inhaler (MDI)

A metered dose inhaler is a device that delivers a specific amount of medication to the lungs in
the form of a short burst of aerosolized medicine that is usually self-administered by the patient
via inhalation. It is the most commonly used delivery system for treating asthma, COPD and
other respiratory disease.

 Used to minimize the number of administration errors.

 To improve the drug delivery of aerosolized particles into the nasal passageways and
respiratory tract.
Advantages of MDI:
 It delivers specified amount of dose.
 Portable and compact.
 Quick to use, no contamination of product.
 Dose-dose reproducibility is high.
Disadvantages of MDI:

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  Low lung deposition; high pharyngeal deposition.
 Coordination of MDI actuation and patient inhalation is needed.
Marketed pharmaceutical aerosol products:
Metered Dose inhalers:
Drug Use
Fluticasone Asthma
Fluticasone and Salmeterol Asthma
Flunisolide Asthma
Beclomethasone Asthma
Albuterol Bronchospasm

Parenteral products

Sterile Products: Sterile products are dosage forms of therapeutic agents that are free from
micro-organisms or their spores.
Parenteral Products: Parenteral products are sterile dosage forms that are injected into body
tissues (into internal body compartment) through one or more layers of skin or mucous
membrane. Therefore, they must be exceptionally pure and free from physical, chemical and
biological contaminants.
Basic requirements of parenteral products:
1. Parenteral Products must be free from viable micro-organisms or their spores.
2. They must be free from toxic components/pyrogen.
3. All components and process involved in the preparation of these products must be
selected and designed to eliminate contaminants of all types such as physical, chemical and
microbiological contaminants.
4. The product must be free from non-dissolving particulate materials. The Product must be
clear.
5. The products must be free from pyrogens.
6. Safety level of all the ingredients should be same and every means of safety should be
ensured including packaging material.
7. The product must be chemically stable over a long period of time.
8. The pH of the product should be strictly maintained. Adequate buffers should be used.
9. Water used in parenteral products must be free from pyrogens.
10. A non-aqueous solvent must be selected.
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11. Isotonicity of the product must be maintained.
12. Container of the parenteral products must be inert/sterilized.
13. Water for injection should have conductivity < 1μmho.

Advantages of parenteral products:

1. Actual and accurate administration of the dose can be maintained by a professionally

skilled person.
2. It is a highest purity product.
3. Its immediate physiological action is needed from a drug. It usually can be provided by
the intravenous injection of an aqueous solution.
4. They have often a lifesaving advantage in emergencies due to their rapidity of action.
5. Drugs can be administrated parenterally, whereas they are not given orally because of-
 Unconscious or uncooperative state of the patient.
 Intestinal inactivation by the enzymatic action.
 Lack of absorption in the intestinal tract.
6. Parenteral products escape the first pass effect of the drug.
7. This route of administration is applicable for both short life drug by infusion and
longtime drug by implantation.
8. Valuable in supplying total parenteral nutrition (T. P .N) in coma patients.
9. Bioavailability is very high.
10. Drugs used for immunization and diagnostic purpose are given through this route.
11. Localized action can be activate.
12. Modification of the formulation or another route of injection can be used to slow the
onset and prolong the action of the drug.

Disadvantages of parenteral products:

1. The requirement of skilled person for administration of the drug in this route.
2. The requirement of asepsis at administration.
3. It is considerably more expensive.
4. Causes physical disturbances, discomfort or fear of patient during administration.
5. They are risk of tissue toxicity, rapid occurrence of allergic reactions and anaphylactic
shock in sensitive individuals which are harmful and sometimes fatal.

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 6. Little contamination both with product and accessory equipment causes fatal diseases.
7. Not reproducible.
8. Difficulties in correcting an error.
9. Daily on frequent administration poses difficulties for the patient to visit a
professionally trained person or to learn inject on-self.
10. Packaging, filling, sealing and transportation are somehow tough and need special care.

Classification of parenteral products

Classification of parenteral products:

(A) On the basis of origin

(B) According to USP & NF

(C) According to BP

(D) Route of administration

(E) Intrabursal route

(F) Intraperitonial rout

(A) On the basis of origin

ON THE BASIS OF
ORIGIN

ORIGIN

BIOLOGICALS NON-BIOLOGICALS

 VACCINES ALL TYPES OF

 VITAMINS
 HORMONES SYNTHETIC AND
 ANTI-TOXINS
SEMI-SYNTHETIC
----NATURAL ANTIBIOTIC
PRODUCTS.

EXAMPLE-MORPHIN
INJECTION,

PHENOBARBITONE

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(B) According to USP and NF:
(1) Solution: E.g. Adrenaline injection, Ca-gluconate Injection.
(2) Suspension: E.g. Different types of Steroids.
(3) Emulsions: E.g. Vit-K Injection.
(4) Solids which upon addition of liquid form a solution: E.g. Thiopentone-Na, Vinblastine
sulphate.
(5) Solids which upon addition of liquid form a suspension: E.g. Procaine penicillin.

(C) According to BP
(1)Injections:
 Suspensions
 Solution
 Emulsion
(2) Intravenous Infusion:
 These are the large vol. of parenterals given in excess of 10ml (or maximum 20ml)
 It is always administrated intravenously. No other route is permitted.
 It is either an emulsion or solution but never be a suspension.
(3) Concentrated solution for injection & IV infusion:
 By means of dilution and using a suitable vehicle injection or intravenous infusion is
prepared from concentrated solution just before the administration.
 Easily transportable.
(4) Powder for Injection
 It is in the dry state excluding the vehicle used for injection.
 It is a solid dosage form.
 It is done for stability.
(5) Implants:
 Implants are in the form of solid plate inserted beneath the skin by skin incision.
 Drug releases slowly.
 Long duration of action.
 It is a sophisticated released dosage form.
(D) According to Route of Administration
Injections are administrated into the body by means of many route of administration. Routes of
administration depends upon various factor such as—
 Nature of product

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  Release of drugs
 Safety
 Onset of action
 Patient Acceptability
 Therapeutic Response
The most important routes are:
(i) Intracutaneous or Intradermal (0.1-0.2 ml)
(ii) Subcutaneous or Hypodermis (1 ml)
(iii) Intramuscular (2-4 ml)

(iv) Intra-arterial INTRAVUSCULAR

1-500 ml
(v) Intra-Venous

(vi) Intracardiac

(vii) Intra-spinal

i. Intracutaneous or Intradermal:(0.1-0.2ml):
 Injections are administrated into the skin between the epidermis and dermis.
 The volume that can be injected is small, usually 0.1-0.2ml due to poor vascularity of the
site which goes poor dispersion of the drug.
 The route is used mainly for diagnostic tests. E.g. test for penicillin.

ii. Subcutaneous or Hypodermis: (1 ml):

 The injections are made under the skin into the subcutaneous tissue. It is employed for
small volume injections (SVI) when it is desired to spread the drug action but over an
extended period.
 The volume injected is usually 1 ml or less.
 The route is not used for aqueous suspensions or oily suspension and fluids.
 It is used usually for self-medication by the patient.
E.g. Insulin or certain mercurial diuretics
iii. Intramuscular Route :( 2-4 ml):
 Injections are made by passing the needle into the muscle tissue via skin, subcutaneous
tissue and membrane enclosing the muscle.
 The volume usually is 2 ml or less but not greater than 4 ml.
 The route is used for aqueous and oily suspensions and oily solutions, since if they were
injected intravenously, blockage of small blood vessels.

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  Here the drug provide a slow onset of action and prolong duration.
iv. Intra-arterial route:
 Intra-arterial route is used for an immediate effect in a peripheral organ. E.g. To
improve circulation to the entremeties when arterial flow is restricted by arterial
spasm or early gangrene. Example- Tolazolin HCl, a peripheral vasodilators.
v. Intra-Venous Route: (1ml---500ml) usually >10ml:
 Substances are introduced directly into the blood stream by the intravenous route.
 The most common site is the median basilica vein at the anterior surface of the elbow.
 The volume can vary from less than 1 ml to in excess of 500 ml .Small volumes
may be administrated for a rapid effect (e.g.anaesthetics) and large(perfusion or
infusion fluids) to replace body fluids , losses in shock ,severe
burns,vomiting,diarrhea.
 The route ensures rapid body dispersion and generally administrations of volumes in
excess of 10 ml is termed intravenous infusions.
 O/W emulsions may be administrated by this route.
Large volume of fluid containing essential electrolytes and nutrients substances can be
administrated only by intravenous route.
vi. Intra-cardiac route:
 This route is used for emergencies condition only when drugs are given directly into
treat muscle on ventricles. Example: Stimulants, such as adrenaline or isoprenaline
sulphate.
vii. Intra-spinal route:
 These routes involve access into or around the spinal cord. Single dose injections, no
greater than 20ml are used. Spinal cord is enclosed in three coats. The outer one is
known as the dura mater, the middle one as the arachnoid and the inner one as the pia
mater. The subarachnoid space lies between the arachnoid and pia mater and contains
CSF.
(a) Intra-athecal or subarachnoid injection:

 Intra-athecal injections are made into the subarachnoid space.

 This route is used for spinal anesthetics and antibiotics such as Streptomycin in the
treatment of tubercular meningitis (Mycobacterium T.B).
 Specific gravity of such injection should maintain as that of CSF so that it won’t be
diffuse into the brain.
(b) Intra-cisternal injection:

 Intra-cisternal injections are made into the cisterna magna, which lies directly below the
medulla. E.g. primarily used to remove CSF occasionally used for antibiotic treatment.
(c) Peridural Injections:

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  These are made into the peripheral space which located between the durameter and the inner
aspect of vertebrae.This space extends throughout the full length of spinal cord.
E.g. localized anaesthetic.
– Injection during child labour.

DURAMATER

PIAMETER ARACHNOID

Subarachnoid
space
SUBARACHNOID INJECTION

viii. Intra-articular route:

Intra-articular injections are made into the synovial fluid which lubricates the articulating ends of
bones in a joint. E.g. specially arthritis gout.
ix. Intra-bursal route:
Intra-bursal injections are given into the bursare which are small sacs of fluids between movable
parts such as tendons and bones.
Ophthalmic route:
 The dose volume is never greater than 1 ml.
 There are four routes-
– Subconjunctival route.
– Intravenous route.
– Intra-cameral route.
– Intraocular route.
x. Intra-peritonial route:
Injections are administrated directly into the peritoneum of the heart.
Other Routes:
– Intra-ossicular route
– Intracerebral
– Intrapleural
– Intra mammary

Opthalmic products

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Opthalmic products: Ophthalmic products are the sterile products meant to instillation in to the
eye in the space between eye lid and the eye ball.
These products must be sterile and are prepared under the same condition and by the same
methods as other parenteral preparations.

Types of Ophthalmic preparation:

Eye drops: Aqueous or oily solutions and suspensions of active medicaments for instillation into
the conjunctival sac. E.g. Chloramphenicol B.P; Neomycin Sulphate B.P.
Eye lotions: These are solutions for the irrigation of the conjunctival sac. They act mechanically
to flush out irritants or foreign bodies as a first aid treatment. E.g. Sterile NaCl 0.9% solution.
Eye ointments: Preparations containing active ingredients for application to the lid margins and
conjunctival sac. E.g. Acyclovir B.P; Polymyxin Sulphate B.P.
Contact lens solutions: Aqueous solutions for lubricating, cleaning and hydrating contact
lenses.
Ophthalmic inserts: Solid dosage forms placed in the conjunctival sac and designed to release
active ingredients over a prolonged period.

Implants
Implants: Implants are drug-bearing polymeric device which are implanted subcutaneously or in
various body cavities. This is one of the oldest and most highly developed forms of drug
delivery. This method finds particular applicability to cases where chronic administration of drug
over period ranging from days to years is required.
Examples includes: Insulin for diabetes, Pilocarpine for glaucoma, Immune agents for various
diseases and allergies, Contraceptive steroids, Narcotic antagonists.
There are four types of implantable devices based on the site of implantation.
These include:
1. Subcutaneous device
2. Intravaginal devices
3. Intrauterine devices
4. Intraocular devices

Suppositories

Suppositories: The derivation of the word “Suppository” is form the latin “Supponere” meaning
“to place under” as derived from sub (under) and ponere (to place). Suppositories are solid

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dosage forms intended for insertion into body orifices where they melt, soften or dissolve and
exert localized or systemic effects.
Advantage of suppository:
 It is the alternated dosage form for drugs which have less bioavailability when it is taken
orally.
 Drugs having bad odour and taste can be used in suppository form.
 It is suitable for unconscious patients which cannot taken drugs orally.
 It is suitable for drugs which produce irritating effect in GIT.
 It is suitable for infants and old people who find difficulty in swallowing of drugs.
 It is suitable for the drugs which are destroyed by portal circulation.
Disadvantage of suppository:
 The manufacturing process is more difficult as compare other formulation.
 The drugs which cause irritation to mucous membrane cannot be administrated by this form.
 The most important problem is storage condition because it stored at low temp.(10-20°C).
Other than the bases get liquefied.
 Leakage problem is also most critical problem along with suppository after introducing in
body cavity at elevated temperature.
Types of suppository:
Rectal suppositories:
 It is inserted in the rectal.
 The weight of suppository used in children is about 1g and in adult about 2g.
 The shape of suppository used in rectal is torpedo shape. The length is about 3 cm.
Urethral suppositories:
 The weight of this type suppository is about 2g and 60-75 mm long in Females.
 Those intended for males weigh 4g each and are 100-150 mm long.
 It is available in pencil shape.
Vaginal suppositories:
 It is in oviform shape.
 It is about 3-5gm in weight.
 It is contains the drugs which are used in treatment of the infections of female genitourinary
tract and meant for contraception.
 It is contains the combination of polyethylene glycol of different molecular weights as
suppository bases.

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 Packaging

Packaging is the science, art and technology of enclosing or protecting products for distribution,
storage, sale and use. Packaging may also be defined as the collection of different components
(e.g. bottle, vial, closure, cap, ampoule, and blister) which surround the pharmaceutical product
from the time of production until its use.

Characteristics of packaging:
The material selected must have the following characteristics:
 Must meet tamper-resistance requirements
 Must be FDA approved
 Must be non-toxic
 Must not impart odor/taste to the product
 Must not reactive with the product
 They must protect the preparation from environmental conditions
Types of packaging:
Primary packaging: The material that first envelops the product and holds it. E.g.Ampoules,
Vials, Containers, Dosing dropper, Closures (plastic, metal), Syringe, Strip package, Blister
packaging.
Secondary packaging: Outside the primary packaging – perhaps used to group primary
packages together. E.g. Paper and boards, Cartons, Corrugated fibers, Box manufacture).
Tertiary packaging: Used for bulk handling, warehouse storage and transport shipping. The
most common form is a palletized unit load that packs tightly into containers.
Types of packaging material:
 Glass
 Plastics
 Rubbers
 Paper/card boards
 Metals
Glass:
Glass has been widely used as a drug packaging material.
Advantages of glass:
 They are transparent.
 They have good protection power.
 They can be easily labelled.

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  Economical.
 Variety of sizes and shapes.
Disadvantages of glass:
 Glass is fragile so easily broken.
 Release alkali to aqueous preparation.
Types of glass:
Type I—Highly resistant borosilicate glass.
Type II—Treated soda lime glass.
Type III—Soda lime glass.
Type IV (General purpose soda lime glass).

Plastic:
Plastics may be defined as any group of substances, of natural or synthetic origins, consisting
chiefly of polymers of high molecular weight that can be moulded into a shape or form by heat
and pressure.
Advantages of plastic:
 Less weight than glass.
 Flexible.
 Variety of sizes and shapes.
 Essentially chemically inert, strong, rigid safety use, high quality, various designs.
 Extremely resistant to breakage.
Disadvantages of plastic:
 Absorption permeable to moisture
 Poor printing, thermostatic charge
Types of plastics:
Thermosetting type –
 When heated they may become flexible but they do not become liquid. E.g. Urea
formaldehyde (UF), Phenol formaldehyde, Melamine formaldehyde (MF), Epoxy resins
(epoxides), Polyurethanes (PURs).
Thermoplastics type-
On heating they are soften to viscous fluid which harden again on cooling. E.g.
Polyethylene{HDPE – LDPE}, Polyvinylchloride(PVC),Polystyrene Polypropylene, Nylon(PA),

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Polyethylene terephthalate (PET) ,Polyvinylidene chloride(PVdC), Polycarbonate Acrylonitrile
butadiene styrene(ABS).
Metals:
Metals are used for construction of containers. The metals commonly used for this purpose are
aluminium, tin plated steel, stainless steel, tin and lead

Advantages of metals:
 They are impermeable to light, moisture and gases.
 They are made into rigid unbreakable containers by impact extrusion.
 They are light in weight compared to glass containers.
 Labels can printed directly on to their surface.
Disadvantages of metals:
 They are expensive.
 They react with certain chemicals.
Rubber:
Rubber is used mainly for the construction of closure meant for vials, transfusion fluid bottles,
dropping bottles and as washers in many other types of product.
Butyl rubber:
Advantages:
 Permeability to water vapour.
 Water absorption is very low.
 They are relatively cheaper compared to other synthetic rubbers.
Disadvantages:
 Slow decomposition takes place above 130 ° C.
 Oil and solvent resistance is not very good.
Nitrile rubber:
Advantages:
 Oil resistant due to polar nitrile group. Heat resistant.
Disadvantages:
 Absorption of bactericide and leaching of extractives are considerable.
Chloroprene rubber:
Advantages: Oil resistant. Heat stability is good.

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Silicon rubber:
Advantages:
 Heat resistance.
 Extremely low absorption and permeability of water.
 Excellent aging characteristic.

Disadvantages:
 They are very expensive.
Tamper resistant packaging:
 The requirement for tamper resistant packaging is now one of the major considerations in the
development of packaging for pharmaceutical products.
 Tamper resistant package is one having an indicator to entry in which, if missing, can
reasonably be expected to provide visible evidence to consumers that tampering has
occurred.
 FDA approves the following configurations as tamper resistant packaging: Film wrappers,
Blister package, Strip package, Bubble pack, Shrink seals, and bands Oil, paper, plastic
pouches, Bottle seals, Tape seals, Breakable caps, Aerosol containers

Strip pack

A strip package is a form of unit dose packaging that is commonly used for the packaging of
tablets and capsule. A strip package is formed by feeding two webs of a heat sealable flexible
through heated crimping roller. The product is dropped into the pocket formed prior to forming
the final set of seals. A continuous strip of packets is formed in general. The strip of packets is
cut into desired number of packets. Different packaging materials used are:
paper/polyethylene/foil/PVC.

Blister pack

Blister package provides excellent environmental protection and efficacious appearance. It also
provides user functionality in terms of convenience, child resistance and tamper resistance.
The blister package is formed by heat softening a sheet of thermoplastic resin and vacuum
drawing the soften sheet of plastic into a contoured mould. After cooling the sheet is released
from the mould and proceeds to the filling station of the machine. It is then lidded with heat
sealable backing material. Peel able backing material is used to meet the requirements of child
resistance packaging. The material such as polyester or paper is used as a component of backing
lamination. Materials commonly used for the thermo formable blister are PVC, polyethylene
combinations, polystyrene and polypropylene.

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 Clean Room

Clean room: A clean room can be defined as an environment where the supply, distribution
and filtration of clean air and the material of construction are regulated to meet the appropriate
cleanliness levels required and defined by the governing authorities to execute a validatible clean
room.
Sources of contamination:
Possible sources of contamination are –
1. Atmosphere
2. Operator
3. Raw materials
4. Equipment

1. Atmosphere:
Atmosphere is invariably heavily contaminated with particles and microorganisms.
a) Contaminants in outside air:
Originate from soil and carry soil organisms including-
1. Bacteria spores (Bacillus spp, Clostrium spp)
2. Mould spores (Penicillium, Mucour, Aspergilius)
3. Yeasts
4. Micrococci
b. Contaminants in indoor air:
1. Originate from human body and clothing’s-
2. Bacteria spores on human skin (Staphylococcus spp, Streptococcus spp)
3. These will also occur in droplets expelled out into the air from respiratory tract by
talking, coughing, sneezing etc.
2. Operator (Most risky factor):
The skin, hair and clothing of the operator are potent sources of particulate and microbial
contamination. Organisms found on the skin and transmitted on the skin particles are –
Staphylococcus.
Diphtheroids.
Lipophillic yeasts.
Dermatophytic fungi.
3. Raw materials:
1. Drugs which are obtained from natural sources
Example: Plant source – saprophytic bacteria, yeast, moulds; Animal source –pathogenic
bacteria / spores.
2. Packaging materials and closures contaminate specially the parenteral solutions.
3. Pigments: Salmonella
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4.Starches: Coliforms
5.Gums: Actinomyces
6.Water – prime source of particulate contamination
4. Equipment: During their preparation and processing they may generate dusts from
atmosphere, particles and droplets may be sedimented on to the internal and external surface of
equipment.
Typical system for supplying clean air:
1. Intake of fresh air
2. Prefiltration
3. Temperature adjustment
4. Humidification
5. Final filtration
1. Intake of fresh air: As most of the pathogen-containing dust particles are found at street level
or ground level, so air should be collected as possible as from upper level.
2. Prefiltration: This consists of a coarse filtration to remove large particles to protect the main
filter.
3. Temperature adjustment: The air is passed over coils through which steam or refrigerant is
circulated to permit thermostatic control of the air temperature.
4. Humidification: The air is passed through a fine atomized spray of demineralized water to
increase the humidity to an acceptable level. Drying of air is achieved by-
 Passing it over the beds of desiccant
 Condensing the vapor in a cooling unit
5. Final filtration: It is achieved by using a “High Efficiency Particulate Air” (HEPA) filter,
positioned at or as close as the inlet to the room.
Types of clean room (On flow):
There are two basic types of clean room; these are identified by the method of ventilation,
namely the non-unidirectional type (sometimes called conventional turbulent) and the more
effective unidirectional type (sometimes called laminar flow). The unidirectional type can
be divided into cross flow and down flow.
Difference between non-unidirectional and unidirectional clean room:
 Non-unidirectional clean rooms have a ventilation supply system similar to that found in
offices and shops where ceiling diffusers supply filtered, conditioned air which mixes and
dilutes the contaminated room air.
 Unidirectional clean rooms are ventilated through a complete ceiling or wall of high
efficiency filters. The velocity is usually about 0.30 m/s in down flow rooms and 0.45 m/s in
cross flow.

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 Mixed flow systems

Mixed flow systems: Mixed flow systems are used in most pharmaceutical applications. The
ventilation of the background room area is non unidirectional whereas in the critical area, where
the product is open to contamination, airflow is unidirectional. There has, however, been a trend
towards protecting the critical area with isolators. Isolators give almost complete protection from
room contamination as they are positively pressurized with air supplied through high efficiency
air filters. The operator works outside the system using glove ports to make contact with the
containers and the filling and sealing machinery.
Pharmaceutical clean room classification:
EU cGMP
Maximum permitted number of particles/m3 equal to or above
Grade At rest (b) In operation
0,5 𝜇m 5𝜇m 0,5 𝜇m 5,0 𝜇m
A 3500 0 3500 0
B(a) 3500 0 350000 2000
C(a) 350000 2000 3500000 20000
D(a) 3500000 20000 not defined (c) not defined (c)

Air classification by USFDA guideline on sterile drug products.

Clean area < 0.5𝜇m < 0.5𝜇𝑚 particles/ Microbiological limit
classification particles/ft3 mt3 Cfu/ft3 cfu/m3

100 100 3500 <1<3

1000 1000 35000 <2<7
10000 10000 350000 <3 <18
100000 100000 3500000 <25 <88

The top ten issues to consider when designing a clean room are:
1) Clarity about the GMP and standard used.
2) Unidirectional airflow specification qualification.
3) Clean room pressurization.
4) Air change rates and recovery time in non-unidirectional systems.
5) Clean room configuration for the service and maintenance of process.
6) Validation of building control systems.
7) Real time particle monitoring systems.
8) Retest and re-qualification frequently.
9) Bio-decontamination by fumigation.
10) High efficiency particulate air (HEPA) filters leak testing.

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 HEPA filter

High efficiency particulate air (HEPA) filters: High efficiency particulate air (HEPA) filters
are essential to the correct performance of a clean room. It is composed of various fibers (mainly
glass) bonded with resin or acrylic binders. Filter consists of a continuous sheet of filtration
material, placed between each pleat and sealed into rigid metal frame. They are capable to
remove 99.99% of particles < 1 µm. Its filter efficiency is ≥ 99.97% of particles as small as
0.3µm.
New generations of ultrahigh efficiency filters are now available. This can retent 99.99% of
particles at 0.1 µm level.
These are—
 Ultra-retention particle filters (UPLA)
 Very Efficient Particle Air (VEPA) filters

HVAC system
It is the abbreviated form of - Heating, Ventilating, and Air Conditioning, which is a system,
which provides conditioned air by providing Heating Cooling & Ventilation System.
The parameters of HVAC include the following:
 Temperature
 Relative Humidity
 Air Class
 Room to room Pressure Gradient
 Air Quality
 Sound level
Recommended limit of the above HVAC Parameters are mentioned below:
 Temperature: 20±5ºC
 Relative Humidity: It is recommended to maintain RH within 50±5 % in all
manufacturing areas, unless there is any specific recommendation for any special
operation. For example, for Effervescent product manufacturing it is recommended to
maintain the relative humidity around 20%.
 Air Class: As per International standards; i.e. Federal standards, ISO standards; British
standards etc.
 Pressure Gradient: It should be maintained relatively negative unless there is any
special requirements. E.g. For sterile areas.
 Air Quality: It should be Dust and Odor free
 Sound level: It should be maintained within 20 db.
Various components of a typical HVAC system are as follows:
 Air Handling unit (AHU)
 Condensing Unit

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  Chiller
 Centrifugal Pumps
 Cooling Tower
 Ducting & Accessories
 Diffuser
 Return Grill
 Dehumidifier
 Air Filters
 Dust Extractor
 Wet Scrubber for Odor control
 Internal lining of ducts to control the noise level.
HVAC system is needed in pharmaceuticals:
 To maintain specified temperature.
 To maintain specific relative humidity.
 To remove dust particle from production area.
 To maintain proper airflow to the room ensuring that cross-contamination does not
occur.
 To prevent microbial contamination in some are by maintaining particle size within
the tolerance range (using HEPA filters etc.).
Application of HVAC system:
 Labs with hoods, potential hazards.
 Bulk Pharmaceutical Chemical (API) plants handling flammable materials.
 Oral Solid Dosage (OSD) plants where potent product/materials exposed.
 Where high potential of product cross-contamination-segregation.
 Some bio API facilities with exposed potent materials.
Advantages of HVAC system:
 Fresh air supply.
 Increased Comfort.
 Elimination of Condensation.
Disadvantages of HVAC system:
 Expensive to operate, especially when cooling and heating.
 Filter loading very high.
 Frequent replacement.
 Potential need for dust collection/scrubbers/cleanouts.

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 Chapter-Six

Quality control and quality assurance

Quality: Quality is the features and characteristics of a product or service that bear on its ability
to satisfy stated or implied needs. It is a combination of all the characteristics of a product that
determine the degree of acceptability of the product.
According to the American society for Quality, ‘Quality’ can be defined in the following ways:
 Based on customer’s perceptions of a product / service’s design and how well the design
matches the original specifications.
 The ability of a product / service to satisfy stated or implied needs.
 Achieve by conforming to established requirements within an organization.
Criteria for quality: Safety, Potency, Efficacy, Stability, Acceptability, Regulatory compliance.
Five basic points for quality: Safety, Quality, Identity, Potency, Purity.

Quality Control

Quality Control (QC): Checking or testing that specifications are met or the regulatory process
through which the industry measures actual quality performance, compares it with standards, acts
on the difference. It is the operational techniques and activities that are used to fulfill
requirements for quality.
QC=Testing + Assessment.
Basic requirements of quality control:
 The finished products containers must comply with specification.
 Approved procedures.
 Correct sampling methods.
 Trained personnel.
 Validation testing methods.
 Product label checks.
 Records are kept of all sampling, inspecting and testing procedures.
 Sufficient retained samples of starting materials, packaging materials and finished
product.
 All batches are reviewed and released by a qualified person to approval procedures.
Responsibilities of quality control department:
 Ensure precision and accuracy of all testing methods.

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  Sampling adequately for testing purpose (physical, chemical and biological)
 Issuing release, reject or quarantine advice for each batch of raw and packaging
materials.
 Assessment of the intermediate products for further processing.
 Assessment of the bulk products for their release, reprocess and reject etc.
 Calibration and standardization of laboratory equipment.
 Control of laboratory reagents.
 Testing of any return goods.
 Analysis of compliant samples with their corresponding receiving samples.
 Monitoring batch -wise full quality control test records with signature of the persons
who performs the test.

Quality control department

Wet analysis / classical method Instrumental analysis

Qualitative analysis Gravimetric analysis Volumetric analysis

Chemical tests Flame test

Qualitative Quantitative

QC Instruments
 HPLC (High performance liquid chromatography)
 GC (Gas chromatography)
 AAS (Atomic absorption spectroscopy)
 UPLC (Ultra performance liquid chromatography)
 FTIR (Fourier transform infrared spectroscopy)
 UV-visible spectrophotometer
 Autoclave

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  Fume hood
 Polarimeter
 Incubator
 Melting point apparatus
 Viscometer
 TLC
 XRD (X-ray diffraction)
 Centrifuge machine
 Microscope
 Turbidity meter
 Vortex mixer
 Osmometer
 Balance
 Dissolution tester
 Disintegration tester
 Conductivity meter
 Spectrophotometer
 Pack integrity tester
 Tablet friability tester
 Tablet hardness tester
 Tab density meter
 Refractometer
 Moisture analyzer
 pH meter
 Karl Fisher titrator
 Potentiometric titrator
 Electronic heating mantle
 Muffle furnace

Lambert’s law

Lambert’s law: This law relates the absorption capacity to the thickness of the absorbing
medium. According to this law, when a monochromatic radiation or light passes through a
homogenous transparent medium the rate of decrease of intensity of radiation with the thickness
of the absorbing medium is directly proportional to the intensity of the incident light.

Beer’s law

Beer’s law: Absorption of light passing through a solution is proportional to the concentration of
drug in the solution. According to the law, when a monochromatic radiation or light passes
through a homogenous transparent medium the rate of decrease of intensity of radiation with the

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concentration of the solute in that system is directly proportional to the intensity of the incident
light.

Beer-Lambert law

The Beer-Lambert law states that the absorbance of a solution is directly proportional to the
concentration of the absorbing species in the solution and the path length. Thus, for a fixed path
length, UV/Vis spectroscopy can be used to determine the concentration of the absorber in a
solution. It is necessary to know how quickly the absorbance changes with concentration.
The general Beer-Lambert law is usually written as:
A=abc
A = Absorbance (optical density)
b= length of sample cell (cm)
c = molar concentration of solute
𝛼= molar absorptivity (molar extinction coefficient)
Limitations of the Beer-Lambert law:
 Interaction with solvent: Hydrogen bonding.
 Scattering of light due to particulates in the sample.
 Changes in refractive index at high analyte concentration.
 Shifts in chemical equilibria as a function of concentration.
 Non-monochromatic radiation, deviations can be minimized by using a relatively flat
part of the absorption spectrum such as the maximum of an absorption band stray light.
 Deviations in absorptivity coefficients at high concentrations (> 0.01M) due to
electrostatic interactions between molecules in close proximity.

Spectroscopy

Spectroscopy: It is the branch of science that deals with the study of interaction of matter with
light.
Principles of Spectroscopy: The principle is based on the measurement of spectrum of a sample
containing atoms / molecules. Spectrum is a graph of intensity of absorbed or emitted radiation
by sample verses frequency (ν) or wavelength (λ). Spectrometer is an instrument design to
measure the spectrum of a compound.
1. Absorption Spectroscopy: An analytical technique which concerns with the measurement of
absorption of electromagnetic radiation. E.g. UV (185 - 400 nm) / Visible (400 - 800 nm)
Spectroscopy, IR Spectroscopy (0.76 - 15 μm).

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2. Emission spectroscopy is a spectroscopic technique which examines the wavelengths
of photons emitted by atoms or molecules during their transition from an excited state to a
lower energy state. Each element emits a characteristic set of discrete wavelengths according
to its electronic structure, and by observing these wavelengths the elemental composition of
the sample can be determined.

UV-Visible spectroscopy
Spectrophotometer: A Spectrophotometer is employed to measure the amount of light that a
sample absorbs. The instrument operates by passing a beam of light through a sample and
measuring the intensity of light reaching a detector.
Ultraviolet-Visible spectroscopy: Ultraviolet-visible spectroscopy or ultraviolet-visible
spectrophotometry refers to absorption spectroscopy or reflectance spectroscopy in the
ultraviolet-visible spectral region. This means it uses light in the visible and adjacent (near-UV
and near-infrared (NIR) ranges.
Principle of Ultraviolet-visible spectroscopy:
Absorption molecules containing 𝜋-electrons or non-bonding electrons can absorb the energy in
the form of ultraviolet or visible light to excite these electrons to higher anti-bonding molecular
orbitals. The more easily excited the electrons, the longer the wavelength of light it can absorb.

Figure: UV-Visible spectroscopy

Applications of Ultraviolet-Visible spectroscopy:
 Qualitative & Quantitative Analysis:
– It is used for characterizing aromatic compounds and conjugated olefins.
– It can be used to find out molar concentration of the solute under study.
 Detection of impurities:
– It is one of the important method to detect impurities in organic solvents.
 Detection of isomers are possible.

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  Determination of molecular weight using Beer’s law.

Fluorescence
Fluorescence is the emission of light by a substance that has absorbed light or
other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has
a longer wavelength, and therefore lower energy, than the absorbed radiation. The most striking
example of fluorescence occurs when the absorbed radiation is in the ultraviolet region of
the spectrum and thus invisible to the human eye, while the emitted light is in the visible region,
which gives the fluorescent substance a distinct color that can only be seen when exposed to UV
light. Fluorescent materials cease to glow immediately when the radiation source stops,
unlike phosphorescence, where they continue to emit light for some time after.

Fluorescence spectroscopy
Fluorescence spectroscopy (also known as fluorometry or spectrofluorometry) is a type
of electromagnetic spectroscopy that analyzes fluorescence from a sample. It involves using a
beam of light, usually ultraviolet light, that excites the electrons in molecules of certain
compounds and causes them to emit light in a very short time, typically, but not
necessarily, visible light. A complementary technique is absorption spectroscopy. In the special
case of single molecule fluorescence spectroscopy, intensity fluctuations from the emitted light
are measured from either single fluorophores, or pairs of fluorophores. Devices that measure
fluorescence are called fluorometers.
Principle of fluorescence spectroscopy:
Molecules have various states referred to as energy levels. Fluorescence spectroscopy is
primarily concerned with electronic and vibrational states. Generally, the species being examined
has a ground electronic state (a low energy state) of interest, and an excited electronic state of
higher energy. Within each of these electronic states there are various vibrational states. In
fluorescence, the species is first excited, by absorbing a photon, from its ground electronic state
to one of the various vibrational states in the excited electronic state. Collisions with other
molecules cause the excited molecule to lose vibrational energy until it reaches the lowest
vibrational state of the excited electronic state. This process is often visualized with a Jablonski
diagram. The molecule then drops down to one of the various vibrational levels of the ground
electronic state again, emitting a photon in the process. As molecules may drop down into any of
several vibrational levels in the ground state, the emitted photons will have different energies,
and thus frequencies. Therefore, by analysing the different frequencies of light emitted in
fluorescent spectroscopy, along with their relative intensities, the structure of the different
vibrational levels can be determined.

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 Figure: Fluorescence spectroscopy

IR Spectroscopy

Infrared (IR) spectroscopy: Infrared spectroscopy is the spectroscopy that deals with the
infrared region of the electromagnetic spectrum, that is light with a longer wavelength and lower
frequency that visible light. It covers a range of techniques, mostly based on absorption
spectroscopy.
Principle of infrared spectroscopy:
Molecules are made up of atoms linked by chemical bonds. The movement of atoms and the
chemical bonds like spring and balls (vibration). This characteristic vibration are called natural
frequency of vibration. When energy in the form of infrared radiation is applied then it causes
the vibration between the atoms of the molecules and when, applied infrared frequency = natural
frequency of vibration, then absorption of IR radiation takes place and a peak is observed.
Different functional groups absorb characteristic frequencies of IR radiation. Hence gives the
characteristic peak value. Therefore, IR spectrum of chemical substance is a finger print of a
molecule for its identification.
IR Frequency Range: The infrared spectrum is divided into three portions, near, mid, and far
infrared, covering wave numbers (related to frequency) from 10-14,000 cm⁻¹. The range 500 -
4000 cm⁻¹ is used for basic laboratory work.
Bonds to H Triple bond Double bonds Single bonds
O-H single bond C≡C C=O C-C
N-H single bond C≡N C=N C-N
C-H single bond C=C C-O
Fingerprint Region
4000 cm-1 2700 cm-1 2000cm-1 1600cm-1 400cm-1

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Application of Infrared (IR) spectroscopy:

 Infrared spectroscopy is a simple and reliable technique widely used in both organic and
inorganic chemistry, in research and industry.
 It is used in quality control, dynamic measurement, and monitoring applications such as the
long-term unattended measurement of CO2 concentrations in greenhouses and growth
chambers by infrared gas analyzers.
 It is also used in forensic analysis in both criminal and civil cases, for example in identifying
polymer degradation.
 It can be used in determining the blood alcohol content of a suspected drunk driver.
 IR-spectroscopy has been successfully used in analysis and identification of pigments in
paintings and other art objects such as illuminated manuscripts.

FTIR

FTIR: Fourier Transform Infrared (FTIR) spectroscopy is a measurement technique that allows
one to record infrared spectra. Infrared light is guided through an interferometer and then
through the sample (or vice versa). A moving mirror inside the apparatus alters the distribution
of infrared light passes through the interferometer. The signal directly recorded, called an
“interferogram”, represents light output as a function of mirror position. A data-processing
technique called Fourier transform turns this raw data into the desired result.
Application of FTIR:
1. Look for the carbonyl C::O strong band at 1820-1660 cm-1.
2. This band is usually the most intense absorption band in a spectrum.
3. If no C::O band is present, check for alcohols.
4. For the broad OH band near 3600-3300 cm-1 and a C-O absorption band near 1300-1000
cm1.
5. If a C::O is present you want to determine if it is part of an acid, an ester, or an aldehydes or
ketones.
6. (Acid ) O-H is present there will also be a C-O single bond band near 1100-1300 cm-1.
Look for the carbonyl band near 1725 -1700 cm-1.
7. (Ester) Look for C-O absorption of medium intensity near 1300-1000 cm-1. There will be no
OH.
8. And continue to interpretate the compound.

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 Chromatography

Chromatography: Chromatography (from Greek chroma ‘color’ and graphein ‘to write’) is the
collective term for a set of laboratory techniques for the separation of mixtures.
Chromatography is an analytical method by which the compounds are separated to their
individual components on the basis of interaction between two phases-one is stationary phase
and another one is mobile phase.
Types of chromatography:
1. Column chromatography: Here mobile phase is poured from top of the column to flow through
the sample present on stationary phase in the column to get separated.
2. High performance liquid chromatography (HPLC): Here mobile phase is pumped into the
column at a defined high pressure and further the column particles are very small so the surface
area is high and better separation takes place.
3. Gas chromatography (GC): Similar to HPLC. Here gas is used as mobile phase.
4. Ion-exchange chromatography: Here the mobile phase is charged and sample molecules with
similar charge present on the charged stationary phase get eluted out as the mobile phase
molecules with charge displace them.
5. Size exclusion chromatography: Here the column is loaded with charged some gel having
pores. Sample particles when poured along with mobile phase has to pass through the sieve like
network of the stationary phase. In doing so, the larger particles elute out first and smaller ones
last. The reason is the smaller ones take longer path in the column stationary phase while larger
particles take short path to elute out.
6. Thin layer chromatography (TLC): Here the stationary phase is a thin layer and plate like.
7. High performance thin layer chromatography (HPTLC): Similar to TLC but more efficient.
8. Paper chromatography: Here column is paper either rectangular or circular.
9. Affinity chromatography: It is a method of separating biochemical mixtures based on a highly
specific interaction such as that between antigen and antibody, enzyme and substrate, or receptor
and ligand.
10. LC-MS: Liquid chromatography combine with Mass spectroscopy (detector).
11. GC-MS: Gas chromatography combined with Mass spectroscopy (detector).
12. Ultra high performance chromatography (UHPLC).
.
TLC

Thin-layer chromatography (TLC): Thin-layer chromatography is a chromatographic

technique used to separate non- volatile mixtures. Thin-layer chromatography is performed on a
sheet of glass, plastic or aluminium foil, which is coated with a thin layer of adsorbent material,
usually silica gel, aluminium oxide or cellulose. This layer of adsorbent is known as the
stationary phase. After the sample has been applied on the plate, a solvent or solvent mixture

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(known as the mobile phase) is drawn up the plate via capillary action. Because different
analytes ascend the TLC plates at different rates, separation is achieved.
Measuring Rf (retardation factor) values:
These measurements are the distance travelled by the solvent and the distance travelled by
individual spots. When the solvent front gets close to the top of the plate, the plate is removed
from the beaker and the position of the solvent is marked with another line before it has a chance
to evaporate.
These measurements are then taken:

Distance travelled by Distance travelled by the varies

the solvent substance

The Rf value for each substance is then calculate using the formula:

Distance traveled by substance

Rf =
Distance traveled by solvent
[Rf values: the ratio of distance the compounds travels to the distance the solvent front travels is
called Rf (retardation factor) value.]
Applications of TLC:
 Separating the components of an extract.
 Identifying the isolated compounds
 Determining their purity.

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  To identify the progress of reaction.
 Analyzing ceramides and fatty acids.
 Detection of pesticides or insecticides in food and water.
 Analyzing the dye composition of fibers in forensics.
 Assaying the radiochemical purity of radiopharmaceuticals
 Identification of medicinal plants and their constituents.
Advantages of TLC:
 Short analysis time.
 All spots can be visualized.
 Adoptable to most pharmaceutics.
 Low cost.
 Uses small quantities of solvent.
 Minimum amount of equipment is needed.
 TLC is very simple to use and inexpensive.
 Reliable and quick.
 More than one compound can be separated on a TLC plate as long as the mobile phase
is preferred for each compound.
 Identification of most compounds can be done simply by checking Rf literature values.
 It is very easy to check the purity using a UV-light.

Liquid chromatography

Liquid chromatography: Liquid chromatography is a chromatographic technique in which the

moving phase is a liquid.

HPLC

High-performance liquid chromatography (HPLC; formerly referred to as high-pressure

liquid chromatography), is a technique in analytical chemistry used to separate, identify, and
quantify each component in a mixture. It relies on pumps to pass a pressurized
liquid solvent containing the sample mixture through a column filled with a solid adsorbent
material. Each component in the sample interacts slightly differently with the adsorbent material,
causing different flow rates for the different components and leading to the separation of the
components as they flow out the column.
Types of HPLC

There are following variants of HPLC, depending upon the phase system (stationary) in the
process:

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1. Normal Phase HPLC:
This method separates analytes on the basis of polarity. NP-HPLC uses polar stationary phase
and non-polar mobile phase. Therefore, the stationary phase is usually silica and typical mobile
phases are hexane, methylene chloride, chloroform, diethyl ether, and mixtures of these. Polar
samples are thus retained on the polar surface of the column packing longer than less polar
materials.
2. Reverse Phase HPLC:
The stationary phase is nonpolar (hydrophobic) in nature, while the mobile phase is a polar
liquid, such as mixtures of water and methanol or acetonitrile. It works on the principle of
hydrophobic interactions hence the more nonpolar the material is, the longer it will be retained.
3. Size-exclusion HPLC:
The column is filled with material having precisely controlled pore sizes, and the particles are
separated according to its their molecular size. Larger molecules are rapidly washed through the
column; smaller molecules penetrate inside the porous of the packing particles and elute later.
4. Ion-Exchange HPLC:
The stationary phase has an ionically charged surface of opposite charge to the sample ions. This
technique is used almost exclusively with ionic or ionizable samples. The stronger the charge on
the sample, the stronger it will be attracted to the ionic surface and thus, the longer it will take to
elute. The mobile phase is an aqueous buffer, where both pH and ionic strength are used to
control elution time.

Instrumentation of HPLC:

As shown in the schematic diagram in Figure above, HPLC instrumentation includes a pump,
injector, column, detector and integrator or acquisition and display system. The heart of the
system is the column where separation occurs.
Applications of HPLC:
Pharmaceutical:
 Tablet dissolution of pharmaceutical dosage.
 Shelf life determinations of pharmaceutical products.
 Identification of counterfeit drug products.

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  Pharmaceutical quality control.
Environmental
 Phenols in drinking water.
 Identification of diphenhydramine in sediment samples.
 Estrogens in coastal waters- The sewage source.
 Environmentally relevant bacteria.
Clinical
 Quantification of DEET in human urine.
 Analysis of antibiotics.
 Increased urinary excretion of aquaporin 2 in patients with liver cirrhosis.
 Detection of endogenous neuropeptides in brain extracellular fluids.
Food and flavor
 Ensuring soft drink consistency and quality.
 Analysis of vicinal diketones in beer.
 Sugar analysis in fruit juices.
Advantages of HPLC:
 Separations fast and efficient (high resolution power).
 Continuous monitoring of the column effluent.
 It can be applied to the separation and analysis of very complex mixtures
 Accurate quantitative measurement.
 Repetitive and reproducible analysis using the same column.
 Adsorption, partition, ion exchange and exclusion column separations are excellently
made.
 Both aqueous and non-aqueous samples can be analyzed with little or no sample
pretreatment.
 A variety of solvents and column packing are available, providing a high degree of
selectivity for specific analysis.
 It provides a means for determination of multiple components in a single analysis.

GC

Gas chromatography: Gas chromatography (GC) is a common type of chromatography used in

analytical chemistry for separating and analyzing compounds that can be vaporized without
decomposition.
Principle of GC: The sample solution injected into the instrument enters a gas stream which
transports the sample into a separation tube known as the “column” (Helium or nitrogen is used
as the so-called carrier gas.). The various components are separated inside the column. The
detector measures a sample with an unknown concentration, a standard sample with known

215
concentration is injected into the instrument. The standard sample peak retention time
(appearance time) and area are compared to the test ample to calculate the concentration.

Advantage of GC:
 Very high resolution power, complex mixtures can be resolved into its components by this
method.
 Very high sensitivity with Thermal conductivity detector (TCD), detect down to 100 ppm.
 It is a micro method, small sample size is required.
 Fast analysis is possible, gas as moving phase- rapid equilibrium.
 Relatively good precision & accuracy.
 Qualitative & quantitative analysis is possible.
Applications of GC:
GC is capable of separating, detecting & partially characterizing the organic compounds,
particularly when present in small quantities.
 Qualitative analysis:
– Retention time is used for the identification & separation.
 Checking the purity of a compound:
– Compare the chromatogram of the std. & that of the sample.
 Quantitative analysis:
– It is necessary to measure the peak area or peak height of each component.
 Used for analysis of drugs & their metabolites.

Paper chromatography

Paper chromatography: Paper chromatography is one the most common type of

chromatography. It uses a puttie of paper as the stationary phase. Capillary action is used to pull
the solvents up through the paper and separate the solute. Paper chromatography is a procedure
used to separate substances in a mixture.

216
Principle of paper chromatography: A small concentrated sample of a mixture is placed on the
chromatographic paper above the line of a solvent mixture. The paper is contact with a solvent
solution at its bottom. This solvent moves through the paper due to capillary action and dissolves
the mixture spot. Some parts of the solvent mixture to be separated have a greater attraction for
the chromatography paper, so they move a greater lesser distance, while other parts of the
solvent mixture have a lesser attraction, so they move a greater distance up the paper.

Column chromatography

Principle of column chromatography: When a mixture of components dissolved in the mobile

phase is introduced into the column, the individual components move with different rates
depending upon their relative affinities. The compound with lesser affinity towards stationary
phase moves faster and it is eluted out of the column first. The one with greater affinity towards
stationary phase moves slower down the column and hence it is eluted latter. Thus the
compounds are separated.
Application of column chromatography:
 Separation of mixture of compounds.
 Removal of impurities or purification process.
 Isolation of active constituents.
 Isolation of metabolites from biological fluids.
 Estimation of drugs in formulation or crude extracts.
Advantage of column chromatography:
 Any type of mixture can be separated by column chromatography.
 Any quantity of the mixture can also be separated.
 Wider choice of mobile phase.
 In preparative type, the sample can be separated and reused.
 Automation is possible.

Disadvantage of column chromatography:

 Time consuming method.
 More amount of solvents are required which are expensive.
Automation makes the technique more complicated and expensive.

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 AAS

Atomic absorption spectroscopy: In analytical chemistry, atomic absorption spectroscopy is a

technique for determining the concentration of a metal element in a sample. The technique can
be used to analyze the concentration of over 70 different metals in a solution. Although atomic
absorption spectroscopy dates to the nineteenth century, the modern form was largely developed
during the 1950s by a team of Australian chemists. They were led by Alan Walsh.
Principle of AAS: Atomic absorption spectroscopy is an analytical technique which has been
developed primarily for the determination of metals at low levels of concentrations.
The technique makes use of absorption spectrophotometry to assess the concentration of an
analyte (solute) in a sample. It relies therefore on Beer-Lambert law. It is based on the absorption
by the free atoms. Atomic absorption takes place when unexcited atoms absorb energy and
become excited atoms. Absorption is therefore carried by unexcited atoms whereas emission
arises from excited atoms.
In short, the electrons of the chemical elements in the atomic state in the atomizer can be
promoted to higher orbital for a short amount of time by absorbing a set quantity of energy (i.e.
light of a given wavelength). This amount of energy (or wavelength) is specific to a particular
electron transition in a particular element and in general, each wavelength corresponds to only
one element. This gives the technique its elemental selectivity for analysis of metals. As the
quantity of energy (the power) put into the flame is known and the quantity remaining at the
other side (at the detector) can be measured, it is possible, from Beer-Lambert law (A = abc, A α
C), to calculate how many of these transitions took place, and thus get a signal that is
proportional to the concentration of the element being measured.
Advantages of AAS:
 Widespread application.
 High sensitivity.
 Good accuracy.
 Freedom from interference.
 Independent of flame temperature and absorption wavelength region.
 Simplicity in operation.
 Moderate cost.
Disadvantages of AAS:
 Does not determine non-metals.
 Does not analyze solid or gas samples directly.
 Determine only one element at a time.
 Anionic interference.
Application of AAS:

218
Determination of even small amounts of metals (lead, mercury, calcium, magnesium, etc) as
follow:
 Environmental science.
 Food technology.
 Pharmaceutical industry.
 Petrochemicals.
 Geochemical.
 Bio-monitoring.
 Agricultural.
 Nanomaterials.
 Pathology.

NMR

NMR: As it is implied in the name, NMR is concerned with magnetic properties of certain
atomic nucleus. Notable are the nucleus of the hydrogen atom - the PROTON,1H - and that of
13
C isotope of CARBON. NMR spectroscopy is a physical technique that permits the exploration
of a molecule at the level of the individual atoms and afford information concerning the
environment surrounding the atom. NMR is a physical phenomenon based upon the quantum
mechanical magnetic properties of an atom’s nucleus. It is a powerful technique that can provide
detailed information on the topology, dynamics and three-dimensional structure of molecules in
solution and the solid state.
Principle of NMR: The principle behind NMR is that many nuclei have spin and all nuclei are
electrically charged. If an external magnetic field is applied, an energy transfer is possible
between the base energy to a higher energy level (generally a single energy gap). The energy
transfer takes place at a wavelength that corresponds to radio frequencies and when the spin
returns to its base level, energy is emitted at the same frequency. The signal that matches this
transfer is measured in many ways and processed in order to yield an NMR spectrum for the
nucleus concerned.
Application of NMR:
 NMR is used in biology to study the bio fluids, cells, perfused organs and bio
macromolecules such as Nucleic acids (DNA, RNA), carbohydrates proteins and peptides.
And also labeling studies in biochemistry.
 NMR is used to determine the structure of molecules.
 NMR is used in physics and physical chemistry to study high pressure diffusion, liquid
crystals, liquid crystal solutions, membranes, rigid solids.
 NMR is used in food science.
 NMR is used in pharmaceutical science to study pharmaceuticals and drug metabolism.
 NMR is used in chemistry to:
– Determination the enantiomeric purity.
– Elucidate chemical structure of organic and inorganic compounds.
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 – Macromolecules- ligand interaction.
 Anatomical imaging.
 Measuring physiological functions.
 Flow measurements and angiography.
 Tissue perfusion studies.
 Tumors.

TOC
 TOC
Total organic carbon (TOC): Total organic carbon (TOC) is the amount of carbon bound in
an organic compound or material derived from decaying vegetation, bacterial growth, and
metabolite activities of living organisms or chemicals.
 Inorganic Carbon (IC):
Carbon that is not present as organic compounds, principally carbonate minerals such as
carbonate, bicarbonate, dissolved carbon dioxide, etc.
Total carbon = TOC+IC

Karl-Fischer Titration

Karl Fisher was the scientist who in 1935 develop the original Karl Fisher method for
determination using pyridine, sulfur dioxide and iodine.
Karl Fisher titration: A Karl Fisher titration determines the water content in a sample, based on
an iodine/iodine redox reaction.
It is a titration method where water reacts with iodine until the water is consumed and the
endpoint is reached.

Step 1: SO2 + MeOH +B MeSO3 −+ HB+

Step 2: MeSO3 −+ H2O + I2 + 2B MeSO4− + 2HB+ + 2I −
A Karl Fisher moisture determination is advantageous, as compared to a determination based on
weight loss, because KF is not affected by volatile compounds.

pH meter

PH meter: A PH meter is an electronic device used for measuring the PH (acidity or alkalinity)
of a liquid (though special probes are sometimes used to measure the PH of semi-solid
substance). A typical PH meter consists of a special measuring probe (a glass electrode)
connected to an electronic meter that measures and displays the pH reading.

220
 Testing Parameter

Raw materials testing parameters:

1. Description 2. Crystallinity 3. Solubility 4. Melting point 5. Identification 6. Clarity and color
7. Bulk density 8. PH 9. Assay 10. LOD/MC 11. Viscosity 12. Dissolution 13. Appearance of
solution 14. Residue on ignition 15. Chromatographic purity 16. Organic volatile impurities
17. Refractive index 18. Specific optical rotation
Finished product testing parameters:
Tablet:
1. Appearance 2. Length 3. Individual weight 4. Friability 5. Average weight 6.
Disintegration 7. Uniformity of weight 8. Dissolution 9. Uniformity of content 10.
Weight variation 11. Hardness and thickness 12. Relative standard deviation 13. Loss on
drying 14. Width (mm) 15. Assay 16. Content of the active ingredient
Capsule:

1. Appearance 2. Individual weight 3. Average weight 4. Uniformity of weight 5.

Uniformity of content 6. Weight variation 7. Disintegration 8. Assay 9. Relative standard
deviation (RSD)
Oral liquid:
1. Appearance 2. PH 3. Average weight 4. Weight variation 5. Viscosity 6. Relative
standard deviation 7. Sterility 8. Identification of active ingredient 9. Microbial limit 10.
Homogeneity 11. Assay
Aerosol and spray:
1. Appearance 2. Identification of active ingredient 3. Relative standard deviation 4. Leak
test 5. Particle size 6. Pressure test 7. Net content
Injectable dosage form:
1. Appearance 2. Identification of active ingredient 3. Relative standard deviation 4. Leak test
5. Net content 6. Sterility test 7. Viscosity 8. PH 9. Pyrogen test 10. Volume check 11.
Osmolarity 12. Clarity test 13. Assay

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 Hardness of Tablets

Hardness: Tablet requires a certain amount of strength or hardness and resistance to friability to
withstand mechanical shakes of handling in manufacture, packaging and shipping. Hardness
generally measures the tablet crushing strength.
Hardness tester: A device to test the hardness of tablets. By this meter the thickness, diameter
and hardness are tested. The machine works by a sensor. The first reading for diameter, second
for thickness and third for hardness. After taking several data the result are printed by the printer.

Friability

Friability: Friability is the ability of a solid substance to be reduced to smaller pieces with little
effort. Friability is the phenomenon where the surface of the tablet is damage or shown a site of
damage due to mechanical shock.
Purpose: To evaluate the ability of the tablet to withstands the breakage during the
transportation and handling.
Criteria: For tablets with a unit weight equal to or less than 650 mg, take a sample of whole
tablets corresponding as near as possible to 6.5g. For tablets with a unit weight of more than 650
mg, take a sample of 10 whole tablets.
Procedure: The tablets should be carefully dedusted prior to testing. Accurately weight the
tablet sample, and place the tablets in the drum. Rotate the drum 100 times, and removed the
tablets. Remove any loose dust from the tablets as before, and accurately weight. Generally, the
test is run once. If obviously cracked, cleaved, or broken tablets are present in the tablets after
tumbling, the sample fails the test. If the results are difficult to interpret or if the weight loss is
greater than targeted value, the test should be repeated twice and the mean of the three tests
determined. A maximum mean weight loss from the three samples of not more than 1.0% is
considered acceptable for most products.
Percentage of friability of the tablets of a badge can be fine by the following formula: percentage
friability = W1−w2 / W1 × 100
Where, W1 = weight of tablets before testing
W2 = weight of tablets after testing.
Limit:
According to B.P = percentage of friability should be not more than 0.8%.
According to U.S.P = percentage of friability should be not more than 1%.

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Weight variation of tablet:
According to B.P:
Average weight of tablets (mg) Maximum percentage difference allowed
80 or less 10%
80- 250 7.5%
More than 250 5%

According to U.S.P:
Average weight of tablets (mg) Maximum percentage difference allowed
130 or less 10%
130-324 7.5%
More than 324 5%

Disintegration
Disintegration: Refers to the physical process by which a tablet breaks down into fine particles.
In the USP-NF requirements for disintegration time are given in each monograph. These
requirements (for example 15 minutes for uncoated tablets, 30 minutes for film coated tablets
and hard gelatin capsules, 60 minutes for other coated tablets) are generally easily met with the
use of super disintegrate.
Disintegration test (U.S.P): The U.S.P. device to test disintegration uses 6 glass tubes that are 3’’
long; open at the top and 10 mesh screens at the bottom end. To test for disintegration time, one
tablet is placed in each tube and the basket rack is positioned in a 1-L beaker of water, simulated
gastric fluid or simulated intestinal fluid at 37± 2°C such that the tablet remain 2.5 cm below the
surface of liquid on their upward movement and not closer than 2.5cm from the bottom of the
beaker in their downward movement. Move the basket containing the tablets up and down through a
distance 5-6 cm at frequency of 28 to 32 cycles per minute. Floating of the tablets can be prevented
by placing perforated plastic discs on each tablet. According to the test the tablet must disintegrate
and all particles must pass through the 10 mesh screen in the time specified. If any residue remains,
it must have a soft mass.

Dissolution

Dissolution: Dissolution is the process by which a solid drug substance becomes dissolved in a
solvent. It is the processes by which drug dissolves out of a dosage form and is made available
for absorption from the gastro-intestinal tract. In vitro measurements are made in a range of
apparatus types. The requirements for different types of dosage forms are given in each
pharmacopoeia.

223
Dissolution tester: This machine tests the dissolution of the tablet/ capsule in the human
stomach temperatures. There is one motor with changeable rpm and one immersion heater. The
water temperature is kept at 37± 2°C.
Classification dissolution apparatus according to in the U.S.P:
 Apparatus 1 (rotating basket)
 Apparatus 2 (paddle assembly)
 Apparatus 3 (reciprocating cylinder)
 Apparatus 4 (flow-through cell)
 Apparatus 5 (paddle over disk)
 Apparatus 6 (cylinder)
 Apparatus 7 (reciprocating holder)
U.S.P. dissolution apparatus 2 is the most widely used apparatus among these.
Dissolution test stage:
Stage Number of tablets Acceptable range
Stage 1 6 tablets Not less than 5%
Stage 2 6+6 = 12 tablets 15%(but not more than 2 tablets)
Stage 3 12+12 = 24 tablets 5%

Raw material quality control

Raw material quality control: The materials are tested for their desired quality. The active
ingredient must be assayed for quantitative evaluations. The following tests are performed:
1. Identification test of the material.
2. Assay of the drug for its quantitative evaluation on potency.
3. Total ash present in the material.
4. Pyrogen tests for WFI.
5. Glass test on containers.
6. Identity test on rubber closure.
7. Flow properties of powder.
8. Density of powders.
9. Particle count in vehicle.
10. PH of the vehicle etc.

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 In process quality control

In process quality control: The tests that are performed throughout the manufacturing operation
are termed as in process quality control. Those tests must be performed before the filling
operation and include—
1. Recording time and temperature of thermal sterilization of the product.
2. Conductivity test during distillation of WFI.
3. Confirmation of volume of fill in product containers.
4. Confirmation of the count and identity of label for the product.
5. Measurement of pH of the product.

Finished Product Quality Control

Finished Product Quality Control: Finished product quality control means test for products
in the individual dose container which is performed after filling operations. It includes---
 Assay of the drug
 Sterility test
 Pyrogen test
 Clarity test (particulate evaluation)
 Leaker test

Sterility test
All products labeled, sterile product must pass the sterility test after subjecting to an effective
process of sterilization. These tests are performed to detect the presence of viable bacteria, yeast
and fungi.
According to USP, two methods are required to check the sterility of the product.
a) Direct method or culture tube incubation method
b) Indirect method or membrane filtration method

a) Direct method:
In this method the product is placed in culture tube containing suitable culture media. If no
growth occurs in any one of the tube then the sample passes the test.

225
 Culture Media Temp. Incubation
Bacteria Thioglycolate 30°-35°c 7-14 days
Molds and Soyabean-casein digest 20°c-25°c 7-14 days
fungi

b) Indirect method:

The titration method involves the passage of the products through a sterile bacteria or
microorganism retentive membrane filter. Then the membrane filter is cut into two halves and
placed in suitable culture media for bacteria and fungi or molds separately. If no growth occurs,
then the sample passes the test.

Pyrogen test
It is the test for pyrogenic substances in parenteral preparations. Two tests are employed:
1. Biological test (Rabbit test)
2. LAL test (Limulus Amoebocyte Lysate test)
Biological test (Rabbit test):

The USP test is a qualitative test which evaluates the fever response in mature rabbit. Rabbits are
used as test animals because they show rapid physiological response to pyrogen similar to that of
human body. The test involves injection of the test solution into the ear vein of rabbits. The rise
in temperature is measured in rectal route. During a 3 hour period following injection, the
temperature of any individual rabbit must not rise, more than 0.6°c, in order for the samples to
pass.
Phase Individual Collective
1st phase Should not exceed Not more than 1-4°c
(3 rabbits) 0.6°c
2nd phase Should not exceed Not more than 3.6°c
(5 more rabbits 0.6°c
3+5=8 rabbits)

226
Limitation:
Many medicinal agents, if present interfere with the test result due to their antipyretic or other
interfering effects.
 Analgesic products itself lower the Temp.
 Proteins drugs raise Temp.

LAL test

The test involves combining of the test solution with LAL (Limulus Amoebocyte Lysate)
reagent. In the presence of pyrogenic endotoxin from gram negative bacteria, a firm gel is
formed within 60 minutes when incubated at 37°c.
Advantages:
 5 to 10 times more sensitive than rabbit test
 Simpler and more rapid
 Avoid destruction of animal.
 Suitable for blood, immunological products.
Disadvantages:
 protein substances may interfere the test
 respond only to endotoxin from gram negative bacteria

Clarity Test

The objective of clarity test is to prevent the distribution and use of parameters which contain
particulate matter that may be physiologically or pharmacologically harmful to the recipient.
USP Limit:
1) In large volume infusions, USP has established a limit of 50 particles of 10µ and
larger.
2) 5 particles of 25 µm and larger per ml
3) If particle size is >30 µm, the sample is rejected.

227
 Leaker Test

During the sealing of ampoules by infusion, incomplete seal may result. This leaves an open
passage way between the solution and the non sterile environment and the product is
contaminated.
Since .it is not always possible to detect faulty seals by visual inspections, a leaker test is
employed to determine incompletely sealed ampules.

Process:

1. The ampoules to be tested for leakage is placed in a vacuum chamber. The negative pressure is
produced within ampules while the ampule is entirely submerged in a deeply colored dye
solution usually 0.5 to 1% methylene blue.

2. After 30 minutes, the vacuum is sharply released.

3. If any opening is present in the ampules the subsequent atmospheric pressure causes the dye to
penetrate an opening, being visible after the ampules has been washed externally to clear it of
dye.

Assay of the Drug

This is the most important test for product evaluation. Actually this test is done to determine the
amount of active ingredients that can be administered in a single dose. This test depends on the
chemical properties of the ingredients and varies from compound to compound. The test is done
both qualitatively and quantitatively.

Melting point

Melting point: The melting point of a solid is the temperature at which it changes state from
solid to liquid at atmospheric pressure. At the melting point the solid and liquid phase exists in
equilibrium. The melting point of a substance depends on pressure and is usually specified at
standard pressure. When considered as the temperature of the reverse change from liquid to
solid, is referred to as the freezing point or crystallization point.

Temperature

Temperature: A Temperature is a comparative objective measure of hot and cold. It is

measured, typically by a thermometer, through the bulk behavior of a thermometric material,
detection of heat radiation, or by particle velocity or kinetic energy. It may be calibrated in any
of various temperature scales, Celsius, Fahrenheit, Kelvin, etc.

228
Temperature conversion instructions:
The formulas used to convert between temperatures are as follows:
 ℃= (℉- 32)∗ 5/9
 ℉= (℃ ∗ 1.8) + 32
 K= ℃ + 273.15
 ℃= K- 273.15

Temperature condition according to BP:

Sl No. Term Condition
1 Deepfreeze Below -15° C
2 Refrigerator 2-8° C
3 Cold/ Cool 8-15 ° C
4 Room temperature 15-25° C

Temperature condition according to USP/ NF:

Sl No. Term Condition
1 Freezer -20° and -10° C
2 Cold Not exceeding 8°C
3 Refrigerator 2° and 8° C
4 Cool 8° and 15°C
5 Room temperature Temperature prevailing in a working area.
6 Controlled room temperature 20° to 25° or 15° and 30°C
7 Warm 30° and 40°C
8 Excessive heat Above 40°C

Solubility

Solubility: Solubility is the indicative of maximum concentration that can be dissolved in the
solvent to form a saturated solution. Thus it is expressed as grams of solute dissolving in volume
of solvent.
Factors affecting solubility:
Many factors affect the solubility of one substance in another. Such as:
 Forces between particles
 Temperature
 Pressure

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Solubility range according to BP:
Relative expressions Parts of solvent required dissolving 1 parts of
solute
Very soluble Less than 1
Freely soluble From 1 to 10
Soluble From 10 to 30
Sparingly soluble From 30 to 100
Slightly soluble From 100 to 1,000
Very slightly soluble From 1,000 to 10,000
Practically insoluble More than 10,000

Stability study

Stability study: USP defines stability of pharmaceutical product as, “extent to which a product
retains with in specified limits and throughout its period of storage and use (i.e. shelf life).
Objective of stability studies:
 To determine maximum expiration date/ shelf life.
 To provide better storage condition.
 To determine the packaging components.
 To gather information during preformulation stage to produce a stable product.
Advantages of Stability studies
 Assurance to the patient
 Economic considerations
 Legal requirement
Stability Protocol
Study Storage condition Minimum time period
covered by date at
submission
Long term (Ambient) 25℃ ± 2°C 12 months
60% RH ± 5%
Intermediate (controlled) 30℃ ± 2°C 6 months
60% RH ± 5%
Accelerated 40℃ ± 2°C 6 months
75% RH ± 5%

230
 Calibration

Calibration: The set of operations that establish the relationship between values indicated by an
instrument and the corresponding known value of a reference standard is known as calibration.
Calibration is the formal, systematic, and documented proof that the used measuring equipment
indicates the values within established / defined ranges.
Calibration of instruments is done in two ways internal calibration and external calibration.
Internal calibration is done the in-house officials whom have sound knowledge on it. External
calibration is done according to the instructions of the manufacturer and should be done in the
government approved individual or institution.

Calibration of instrument flow chart:

Instrument to be
calibrated Instrument output

Input (whole
measuring range)

Instrument of higher The input volume with

standard known accuracy

Standard Ensure the calibration is

instrument done under the specified
environmental condition

Need of Calibration: The main objectives of calibration services are:

 To maintain quality control and quality assurance in production.
 To comply with requirements of global trade.
 To meet the requirement of ISO guides.
 To promote international recognition.
 For tracking back measurement results to national standards.

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Benefits of Calibration:
 It fulfils the requirements of traceability to national / international standards like ISO 9000,
ISO 14000 etc.
 As a proof that the instrument is working.
 Confidence in using the instruments.
 Traceability to national measurement standard.
 Interchangeability.
 Reduced rejection, failure rate thus higher return.
 Improved product and service quality leading to satisfied customers.
 Power saving.
 Cost Saving.
 Safety.
The Basic Requirements for Calibration:
 Reference / Calibration Standards & other instruments / equipments.
 Controlled Environment Conditions.
 Competence of Calibration Lab personnel.
 Traceability of Reference / Calibration standards.
 Documentation.

Titration

Titration: Titration is a technique to determine the concentration of an unknown solution.

Titration is the slow addition of one solution of a known concentration (called a titrant or titrator)
to a known volume of another solution of unknown concentration (called a titrand or analyte)
until the reaction reaches neutralization, which is often indicated by a color change. Also known
as Titrimetry or Volumetric Titration.
The equivalence point: the point when the reactants are done reacting.
The equivalence point is the ideal point for the completion of titration. At the equivalence point
the correct amount of standard solution must be added to fully react with the unknown
concentration.

232
The end point: it indicates once the equivalence point has been reached. It is indicated by some
form of indicator which varies depending on what type of titration being done. For example, if a
color indicator is used, the solution will change color when the titration is at its end point.
Classification of titration:
1. Precipitation reaction.
2. Redox or oxidation-reduction reaction.
3. Conductometric titration.
4. Potentiometric titration.
5. Amperometric titration.
6. Spectrophotometric titration.
7. Complex formation reaction or complexometry.
8. Neutralization reaction or acidimetry and alkalimetry.

Sample and Sampling

Sample: A portion of a material collected according to a defined sampling procedure. The size
of any sample should be sufficient to allow all anticipated test procedures to be carried out,
including all repetitions and retention samples.
Sampling: The process of taking a small portion from a lot /batch for test and analysis.

Quality Assurance

Quality Assurance (QA): Quality Assurance is the sum of the organized arrangements made
with the object of ensuring that products will be of the quality required by their intended use.
It is a planned and systematic set of activities necessary to provide adequate confidence that a
product or service will satisfy given requirements for quality.
QA = Product design + GMP + QC + Quality goal activities.
Responsibility of Quality Assurance department:
 Ensuring fulfillment of regulatory requirements.
 Establishing specifications and control procedures for all starting materials, intermediates,
and finished products.
 Arranging quality audits visits to suppliers and self-inspection.
 Monitoring of the systems to ensure implementation of GMP and GLP in routine operation.
 Ensuring a suitable product quality review system exists.
 Establishing manufacturing operation of methods and SOPs covering entire operations and
their regular updating.

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  In-process checking of manufacturing operation of production area to ensure compliance
with SOP.
 Ensure appropriate sampling of bulk and finished products as per sampling plan for QC
analysis.
 Verify the rules of GMP and GLP, products safety and hygiene and also personal hygiene
during work in process.
 Train up the personnel as per cGMP and others guidelines.
 Perform and monitor the validation and calibration activities.
 Provide change over clearance in all areas of activities.
 Monitor temperature and humidity in all areas of the plant.
 Handle the non-conformities, customer complaints, change control and deviation
management.
 Perform the management of retention samples.
 Review documents (SOPs, BMR, BPR, QC test report, tags etc.) of batches from time to
time.

Quality Assurance

Quality control Product development Quality compliance

Raw and packaging materials Process validation

Water analysis Documentation
Microbiology Audit (internal, external)
Analytical method validation In process check
Finished product Product stability
Vendor approval Training

Difference between QC and QA:

SL NO. QC QA
1. It is the operational technique and It is planned and systematic set of
activities that are used to fulfill activities necessary to provide adequate
requirements for quality. confidence that a product or service will
satisfy given requirements for quality.
2. QC = Testing + Assessment. QA =Product design +GMP +QC +
Quality goal activities.
3. An activity that verifies if the An activity that establishes and evaluates
product meets pre-defined standards. that process to provide the products.
4. Implements the process. Helps establish process.

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5. QC is the responsibility of the tester. QA is the responsibility of the entire team.
6. Verifies if specific attributes are in a Sets up measurements programs to
specific product or service. evaluate process.
7. QC improves the development of a QA improves the process that is applied to
specified products service. multiple products that will ever be
produced by a process.

Validation

Validation: Validation may be defined as the documented act of providing that any procedure,
process, equipment, material, activity, or system actually leads to the expected results.
Importance of Validation:
 Reduction of quality cost due to fewer reject, retest, recall, rework and for yield
maximization.
 Regulatory compliance.
 Process optimization.
 In contrast to in-process and finished product controls, it is possible, by validation date to
predict in which range system parameters have to be maintained.
 Through validation of a system, the system is controlled, deficiencies are deleted which
otherwise may not have been noticed and most important, an intensive security of the
complete system is conducted.
 Drug safety and thus safety for the patient is improved.
 The system is possibly optimized.
 The probability of a product recall is reduced.
 The validation documentation can be used: for presentation in case of an inspection, - as legal
proof of safety in a product liability case as a document for a marketing authorization
application and a certification.
 Capture the market with better quality product at a lower price.
Classification of Validation:
1. Validation of machine
a) Qualification: Qualification is the formal, systematic and documented proof that equipments
are suitable for the intended process.
b) Calibration: Calibration is the formal, systematic and documented proof that the used
measuring equipment indicates the values within established / defined ranges. The set of
operations that establish the relationship between values indicated by an instrument and the
corresponding known value of a reference standard is known as calibration.

2. Validation of process

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a) Unit process: Process validation is establishing documented evidence that provides a high
degree of assurance that a specific process will consistently produce a product meeting its
predetermined specifications and quality characteristics.
b) Cleaning process: Cleaning process validation is establishing documented evidence that
provides a high degree of assurance that a cleaning process will remove all the contaminants
from equipments and premises so that equipments will not contaminate any product.
c) Analytical process: Analytical method validation is the documented laboratory study of
proving that the performance characteristics of an assay make it fit for the intended analytical
application.

3. Validation of product manufacturing method

a) Prospective process validation: Validation activities from product initiation to full-scale

production is known as Prospective process validation.
b) Retrospective validation: Validation of a manufacturing process of product by analyzing
batch documentation is known as Retrospective validation.
c) Concurrent validation: In-process monitoring of critical processing steps and end-product
testing of current production can provide documented evidence to show that the
manufacturing process is in a state of control. Such validation is known as Concurrent
validation.

Difference between calibration and validation:

Sl CALIBRATION VALIDATION
No.
1. The set of operations that establish the Validation may be defined as the
relationship between values indicated by an documented act of providing that
instrument and the corresponding known value of any procedure, process, equipment,
a reference standard is known as calibration. material, activity, or system
Calibration is the formal, systematic and actually leads to the expected
documented proof that the used measuring results.
equipment indicates the values within established
/ defined ranges.
2. Calibration means system performance checking. Validation means method of
analysis performance checking.
3. In calibration performance of an instrument or No such reference standards are
device is compared against a reference standard. used in validation program.

4. Calibration ensures that instrument or measuring Validation provides documented

devices producing accurate results. evidence that a process, equipment,
method or system produces
consistent results (in other words, it
ensures that uniforms batches are
produced).

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4. Shall be performed periodically, to identify the No such requirements. Shall be
‘drift’ of the measuring device or equipment and performed when changes or
make them accurate. modifications happen to the
existing system or once revalidation
period is reached.
6. Shall be performed as per calibration SOP. Shall be performed as per
validation protocol.

Qualification

Qualification: Qualification is the formal, systematic and documented proof that equipments
are suitable for the intended process and leads to the expected results.
Equipment and facility qualification: Stages of validation
DQ [Design qualification]:
Design Qualification is used at the stage where a design that has been developed from the URS,
is reviewed and documented by competent persons to ensure that the designed equipment, if
built, will satisfy all the detailed specified requirements. The Design Qualification is the only
document that is going to confirm that the design will work. It must be carried out by qualified
people who can challenge the design performance. If you have no such persons on your staff you
must contract them in or contract the DQ out.
IQ [Installation qualification]:
The Installation Qualification (IQ) execution; verifies that the equipment and its ancillary
systems or sub-systems have been installed in accordance with installation drawings and
specifications. It further details a list of all the cGMP requirements that are applicable to this
particular installation qualification. These requirements must all be satisfied before the IQ can be
completed and the qualification process is allowed to progress to the execution of the
Operational Qualification (OQ).
OQ [Operation qualification]:
The documented action of demonstrating that the process equipments and ancillary systems work
correctly and operate consistently in accordance with established specification. Operational
qualification is performed subsequent to installation, after major maintenance or modification of
the instrument, or can be based on a customer quality schedule. The operational qualification
includes a review of the Standard Operating Procedure (SOP’s) for start-up, operation,
maintenance, safety, and cleaning.
PQ [Performance qualification]:

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The normal expectations for PQ are given as requiring, documented verification that facilities,
systems and equipment, as connected together, can perform effectively and reproducibly, based
on the approved process method and product specification. Onto that now should be grafted the
verification that the all the requirements specified in the User Requirements Specification (URS)
have been fully complied.
Differences between Validation and Qualification:
Sl No. Validation Qualification
Validation may be defined as the Qualification is the formal, systematic and
documented act of providing that any documented proof that equipments are
1. procedure, process, equipment, suitable for the intended process.
material, activity, or system actually
leads to the expected results.

Without validation qualification will Without qualification validation will not

2. not complete successfully. complete.

Validation is conducted for a process, Qualification is conducted for equipment,

3. method or system. both (validation and qualification) are
produces a results to meet acceptance
criteria.
Validation is overall process done to Qualification is a subtitle chapter in
4. allow GMP. validation, which covers the instrumentation
documentations, installations.
Validation provides confidence of Word qualification itself shows that the
5. Human, Equipments, Area and process which are adopting for any
Method which are adopted by system scientific process establishment required to
to give consistent results which are be checked with human, equipments, area
predetermined with standard norms. and method are identical similar with
stipulated time, qualified and calibrated call
‘Qualification’

Deviation

Deviation: A deviation is a departure from standard procedures or specifications resulting in

non-conforming material and /or processes or where there have been unusual or unexplained
events which have the potential to impact on product quality, system integrity or personal safety.
For compliance to GMP and the sake of continuous improvement, these deviations are recorded
in the form of Deviation Report (DR).
Deviation must be raised for the following reasons:
 A defect has occurred
 The defect is likely to occur

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  The reason for the defect is unknown
 There is possibility that a defect could occur in the future if the problem is not resolved
 A deviation from the standard operation has occurred
 A system or process is found to be deficient

Change control

Change control: Change control is the system that manages changes that may affect product
quality or the reproducibility of the process.
A written procedure that describes the action to be taken if a change is proposed to facilities,
materials, equipment and/or processes used in the fabrication, packaging and testing of drugs that
may affect the operation of the quality or support system.
Types of change control:
There are two types of change control
1. Planned change (change control): A change that is planned and given the associated lead
time.
2. Unplanned change (deviation system): A change that occurs unexpectedly on an individual
batch or process.

OOS and OOT

OOS (Out of specification): Out-of-specification (OOS) means an examination, measurement,

or test result that does not comply with pre-established criteria.
OOT (Out of Trend): A result that does not follow the expected trend either in comparison with
other batches or with respect to previous results collected during a stability study.
Difference between OOS and OOT:
Sl NO. Out of specification (OOS) Out of Trend (OOT)
OOS stands for Out of Specification, OOT stands for Out of Trend, which
1. which indicates that the specification of exceeds the 80% of the specification
the product will be outside the upper or limit, will be treated as out of trend.
lower limit.

2. OOS needs correction. OOT needs prevention.

OOS related to noncompliance with OOT related to within specification, but
3. specification. having significant variability among the
particular test parameter’s data.
OOS means the batch is failed to meet OOT is product complies to the
4. the specification. specification, however, is out of trend

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 compared to other batches results.
5. OOS is pharmacopeia requirement. OOT is in-house requirement and also
consistency of results represents.

FAT and SAT

FAT: A FAT or Factory Acceptance Test is usually performed at the vendor prior to shipping to
a client. The vendor tests the system in accordance with the clients approved test plans and
specification to show that system is at a point to be installed and tested on site.
It’s an essential aspect of the whole system lifecycle and should be performed by experienced
personnel. Time spent doing a proper FAT will lead to fewer problems when the equipment is
installed on your site.
SAT: A SAT is a Site Acceptance Test the system is tested in accordance to client approved test
plans and specifications to show the system is installed properly and interfaces with other
systems and peripherals in its working environment.

AUDIT

Audit: Systematic, independent and documented process for obtaining audit evidence and
evaluating it objectively to determine the extent to which audit criteria and fulfilled.
First party audit: Internal audit are conducted by or on behalf of the organization itself.
Second party audit: Performed by an organization on their vendor.
Third party audit: Conducted by external independent organizations in order to provide e.g. an
ISO certification, by regulatory agencies to register conformity to standards.

CAPA

CAPA means Corrective and Preventive Action.

Corrective action: Any action to be taken when the results of monitoring at the critical control
point (CCP) indicates a loss of control.
Preventive action: Action to eliminate the cause of a potential non-conformity or other desirable
potential situation.

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Difference between Corrective and Preventive Action
Corrective action Preventive action
Corrective action is taken out on the Preventative action is taken out on the
product/process, system to minimize system/process product to minimize potential
immediate defects or non-conformance. defects or non-conformances recurring.
(Contamination action). (Permanents action).

Root Cause Analysis (RCA)

Root cause: Root cause is the fundamental breakdown or failure of a process which, when
resolved, prevents a recurrence of a problem. For a particular production problem, root cause is
the factor that when you fix it, the problem goes away doesn’t come back.
Root cause analysis: Root cause analysis is a method that is used to address a problem or non-
conformance, in order to set to the ‘Root cause’ of the problem. It is used so we can correct or
eliminate the cause and prevent the problem from recurring. It is a systemic approach to get to
the true root causes of our process problems.

COA

Certificate of Analysis (COA): COA is an important document or paper evidence of the quality
of the drug. It is the evidence of the Quality Control Testing carried out on the drug or
formulation. The Certificate of Analysis (COA) may be defined as a document relating
specifically to the result of testing of a representative sample drawn from the batch of material to
be delivered. Alternatively, COA is an authenticated document, issued by a pharmaceutical
company that certifies the quality and purity of pharmaceuticals (Figure 1.1). The COA does not
only describe the quality but also gives the identity of the drug or formulation. The compliance
statement on COA reveals the specification to which it meets. It must be maintained in the
standard format covering all aspects of the quality in detail.

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 SEU Pharmaceuticals
29/9, Mitford Road
Narayangonj, Bangladesh
Certificate of Analysis (COA)
Generic Name: Paracetamol USP Brand Name: Paramol-S
Product Code:

Batch No. : S00124 Lot No. : SJ502

Manufacturing Date : Nov 11 .2012 Expiry Date: Dec 11. 2012
Stability conditions : Not specified

Analysis Specification Result Test

Description Powder Powder ----
Color White Confirm Organoleptic
Taste Bitter Confirm Organoleptic
Odour Typical Confirm Sensory
Ash value 10.6% 10.6% USP
Moisture content 4.5% 4.4% USP
Assay 98.5% 98.7% USP
Bulk density 12.0 gm per 100ml 11.9% USP
Heavy metals <0.2ppm Confirm Atomic absorption
spectroscopy

Microbiological
Yeast and Mold <500 cfu/gm 100 cfu/gm
A. coli <10 cfu/gm 10 cfu/gm

Compliance:

Signature: Signature:
Name: Y (M. Pharm) Name: X (M.Pharm)
Analytical Pharmacist Director, QC and QA
Date of approval: Batch release date:

Figure: A Model COA

Template/Parts of COA
1) Header: This is first section of COA. This part includes the title “Certificate of Analysis”,
Company name, full address, Pharmacopoeal/trade name of drug/formulation and
Pharmacopoeal designation/category. The header indicates origin and identity of the
drug/formulation.

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2) Body: This part contains lot or batch no., date of manufacture, product code, expiration date,
stability condition and recommended re-evaluation date (if needed). It should also include the
quantity of the material which can be identified by the specific means and other required
information as per demand/need of the customer.
3) Analysis: This part is the heart of the COA. It includes the name of the test carried out, test
results and the acceptance criteria/specifications. The test results should include the actual
data other than the words complies or passes. The test results determine the quality of the
drugs. COA should include all the tests described in particular pharmacopoeal or other non-
pharmacopoeal test performed on the drug/formulation.
4) Certification and compliance statements: This states the compliance of the
drug/formulations with the intended pharmacopoeal. The compliance statement is important
because this is to be based on the results of the analysis. The compliance certificate can be
given if the drug or medicine is manufactured following cGMP or meets all of the
specifications of the intended pharmacopoeal grade.
5) Footer: This part contains the signature, name and designation of the pharmacist/chemist
who has carried out the tests and the authorized person. This section also includes the date of
approval and page number. Actually the dates that are to be mentioned on COA are date of
manufacturing, expiration date, analysis date and batch release date.

Customer Complaint

Customer Complaint: A consumer compliant or customer compliant is an expression of

dissatisfaction on a consumer’s behalf to a responsible party. It can also be described in a
positive sense as a report from a consumer providing documentation about a problem with a
product or service. In fact, some modern business consultants urge businesses to view customer
complaints as a gift.
Types of compliant:
Basically it is three types:
a) Quality complaints: Originate at consumer level and concern with physical, chemical and
biological properties or condition of labeling and packaging of the product.
b) Adverse reaction complaints: Due to allergic reactions of any other unwanted reaction or
fetal reaction or near fatal reaction.
c) Other medically related complaints: Include complaints such as lack of efficacy or clinical
response.

Product Recall

Product Recall: A product recall is a request to return to the market a batch or an entire
production run of a product, usually due to the discovery of safety issues or a product defect.
Recall means a firm’s removal or correction of a marketed product that the Food and Drug

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administration considers to be in violation of the laws it administers and against which the
agency would initiate legal action.
Recall classification:
FDA classified the product recall depending on the health hazard caused by product in the
following way:
Class 1 Recall: A situation in which there is responsible probability that the use of, or exposure
to, a violative product will cause serious adverse health consequence or death.
Class 2 Recall: A situation in which of, or exposure to, a violative product where the probability
of serious adverse health consequences is remote.
Class 3 Recall: A situation in which of, or exposure to, a violative product is not likely to cause
adverse health consequences.

SOP

Standard Operating Procedure (SOP): An authorized written procedure giving instructions for
performing operations not necessarily specific to a given product or material.
Basic components of a SOP:
 Purpose
 Objective
 Scope
 Associated documents
 Definitions
 Abbreviations
 Responsibilities
 Procedure
 Precaution
 Appendix

Benefits of SOP:
 To perform a job properly.
 To ensure that production operations are performed consistently.
 To ensure that processes continued uninterrupted and are completed on a prescribed
schedule.
 To ensure that no failures occurred in manufacturing and other processes for which the SOP
was written.
 To ensure that approved procedures are followed in compliance with company and
government regulations.
 To serve as a checklist for auditors.

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 To serve as an historical record for the changeover.
 To serve as an explanation in review of accident investigations.

Master formula

Master formula: It is document that is used in pharmaceutical manufacturing.

The master formula should include the following information:
 The name of the product
 Description and strength of a product
 Batch size
 A complete test of ingredients
 Quantities of ingredients
 Specification of each ingredients used in the product
 Statements concerning excess
 Theoretical yield
 Manufacturing and control instruction
 Detailed description of closures, containers, labeling and packaging materials.

BMR and BPR

BMR: A batch manufacturing record (BMR) in pharmaceutical industry is information relating

to the product and batch. It is a document that is intended to give a full and authoritative record
of the manufacturing history of each batch of every product.
A typical batch manufacturing record in pharmaceutical industry ideally consists of these details:
 The product name
 Its batch number
 Date on which significant intermediate stage were commenced and completed
 The name of the person who is responsible for each stage of production
 Initials of both operators who carried out significant processes and the persons who checked
these
 Details such as the quantity, batch number, quality control report number of each ingredient
actually weighed, along with the amount of any recovered material that may have been added
 Details of in-process controls, their results and signature of person who performed these
 Details of authorization of any deviation, if any was made
BPR: A Batch Packaging Record (BPR) should be kept for each batch or part batch processed. It
should be based on the relevant parts of the packaging instructions and the method of preparation
of such records should be designed to avoid transcription errors. BPR should be prepared for
each batch of product.

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Each batch processing record should include the following:
 Name of product
 Batch and code number
 Batch formula and brief packaging process
 Packaging data
 Theoretical and actual yield
 Identity of individual major equipment and lines or location used
 Records of cleaning of equipment used for packaging process
 In- process control and laboratory result, such as volume and product weigh
 Packaging line clearance record
 Manufacturing and expiry date
 Any investigation of specific failure or description
 Disposition and identity of quarantine label

PIC and PIC/S

PIC and PIC/S: The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-
operation Scheme (PIC/S) are two international instruments between countries and
pharmaceutical inspection authorities. The PIC/S is meant as an instrument to improve co-
operation in the field of Good Manufacturing Practices between regulatory authorities and the
pharmaceutical industry.
Pharmaceutical Inspection Convention (PIC): A European organization, which mutually
recognizes inspection, reports on manufactures. It is an agreement between the health authorities
of the European Union Member States that they will, on request, with the agreement of the
manufacturers exchange information during their own national inspections of the manufacturing
sites.
Pharmaceutical Inspection Co-operation Scheme (PIC/S): A scheme closely affiliated to the
PIC with identical aims expects mutual recognition. It was created European Community
members who were previously with PIC.

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 Chapter- Seven

Pharmaceutical biotechnology

Biotechnology: Biotechnology is the application of scientific and engineering principles to the

process of materials by biological agents to provide better goods and services.

In another word, Biotechnology is the application of biological organisms, systems and processes
for manufacturing and service industry.

Branches of Biotechnology:
1. Agricultural biotechnology
2. Medical Biotechnology.
3. Engineering biotechnology
4. Biomedical engineering:
5. Textile and paper biotechnology
6. Environmental biotechnology
7. Leather biotechnology
8. Pharmaceutical Biotechnology.

Sub-fields of biotechnology:

There are number of jargon terms for sub-fields of biotechnology.

 Red biotechnology is biotechnology applied to medical processes. An example would

include an organism designed to produce an antibiotic or engineering genetic cures to
diseases through genomic manipulation.

 White biotechnology, also known as grey biotechnology, is biotechnology applied to

industrial processes. An example would include an organism designed to produce a useful
chemical. White biotechnology tends to consume less resources that traditional process when
used to produce industrial goods.

 Green biotechnology is biotechnology applied to agricultural processes. An example

would include an organism designed to grow under specific environmental conditions or in
the presence (or absence) of certain agricultural chemicals. Green biotechnology tends to
produce more environmentally friendly solutions than traditional industrial agriculture. An

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 example of this would include a plant engineered to express a pesticide, thereby eliminating
the need for external application of pesticides.

 The term blue biotechnology has also been used to describe the marine and aquatic
applications of biotechnology, but its use is relatively rare.

Pharmaceutical Biotechnology

 A field that uses micro- and macro-organisms and hybridomas to create pharmaceuticals that
are safer and more cost-effective than conventionally produced pharmaceuticals. This is
major branch of biotechnology which are involved in the production of-

 The therapeutic proteins and hormones, fermentation products like the antibiotics, specially
designed vaccines or drug design using the receptor hypothesis, gene Correction, drug
delivery to specific tissues, production control using Biosensors, standardization of
chemotherapeutic agents and the diagnostic aids by Employing a number of techniques such
as gene cloning technology, recombinant DNA Technology, enzyme immobilization,
fermentation technology, hybridoma technology, Mutagenesis etc.

Difference between biotechnology and pharmaceutical biotechnology:

 Biotechnology is the study of cell and other living organisms for the development of novel
drugs and therapies whereas pharmaceuticals is study of in organic chemical combinations
[do not have life] for the development of drugs or therapies.

 Pharmaceutical biotechnology is (might be) the study of micro- and macro-organisms and
hybridomas to create pharmaceuticals that are safer and more cost-effective than
conventionally produced pharmaceuticals.

Genetic engineering

Genetic engineering, also called genetic modification, is the human manipulation of organisms
genetic material in a way that does not occur under natural conditions. It involves the use of
recombinant DNA techniques, but does not include traditional animal and plant breeding or
mutagenesis.
Any organism that is generated using these techniques is considered to be a genetically modified
organism. The first organisms genetically engineered were bacteria in 1973 and then mice in
1974. Insulin producing bacteria were commercialized in 1982 and genetically modified food has
been sold since 1994.
Genetic engineering, genetic modification (GM), and gene splicing (once in widespread use but
now deprecated) are terms for the process of manipulating genes in an organism, usually outside
of the organism's normal reproductive process.

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It often involves the isolation, manipulation and reintroduction of DNA into model organisms,
usually to express a protein. The aim is to introduce new characteristics to an organism to
increase its usefulness such as, increasing the yield of a crop species, introducing a novel
characteristic or producing a new protein or enzyme. Examples are the production of human
insulin through the use of modified bacteria and the production of new types of experimental
mice like the onco mouse (cancer mouse) for research through genetic redesign.

In short, genetic engineering is the technology of preparing recombinant DNA in vitro by cutting
up DNA molecules and splicing together fragments from more than one organism.

Recombinant DNA technology

Recombinant DNA technology: Recombinant DNA technology refers to a collection of

techniques for creating (and analyzing) DNA molecules that contain DNA from two unrelated
organisms. One of the DNA molecules is typically a bacterialor viral DNA that is capable of
accepting another DNA molecule; this is called a vector DNA. The other DNA molecule is from
an organism of interest, which could be anything from a bacterium to a whale, or a human.
Combining these two DNA molecules allows for the replication of many copies of a specific
DNA. These copies of DNA can be studied in detail, used to produce valuable proteins, or used
for gene therapy or other applications.
Steps involved in the preparation of recombinant DNA:

1. Selection of DNA of interest (foreign DNA).

2. A cloning vector or vehicle to carry inserted pieces of target DNA.
3. Restriction endonucleases which makes internal cuts at specific sites on DNA.
4. DNA ligase: The enzyme that joins pieces of nucleotides/DNA together.
5. A host to replicate the vector containing foreign DNA. This may be prokaryotic
or eukaryotic cell.
6. Screening test for recombinants produced by insertion of DNA.

Schematic diagram of recombinant DNA technology is given bellow:

Taking tissue Taking bacterial cell

Extraction of total RNA Extraction of plasmid DNA by

alkali hydrolysis

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Preparing cDNA by reverse transcription Cutting with restriction enzyme
using reverse transcriptase enzyme
Doing electrophoresis to get appropriate
Taking a small volume of cDNA and amplify plasmid
by PCR using specific primers of target DNA

Doing agarose gel electrophoresis to isolate

the target DNA

Cutting the DNA with restriction enzyme to

get appropriate size

Doing agarose gel electrophoresis to isolate

the target fraction

Target DNA after cutting with restriction

enzyme

Mixing the target DNA with plasmid in presence of DNA lygase (Lygation)

Recombinant plasmid containing target gene

Transformed into host cells (e.g. E.coli)

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 Culturing in an appropriate growth media

Production of target protein

Isolating and purifying the protein by different techniques such as

Extraction, precipitation, chromatography etc.

Measuring the amount of protein by different methods such as Lawry method

Now formulation of proteins using appropriate excipients

Dispensing into unit dosage form.

Gene expression
Gene expression: A gene is the basic unit of heredity in a living organism. It is normally a
stretch of DNA that codes for a type of protein or for an RNA chain. Each cell in the human
body contains about 25,000 to 35,000 genes, which carry information that pass genetic traits to
offspring.

Replication

DNA Transcription
Translation
mRNA
Protein

Figure: Gene expression.

The region of gene that undergoes transcription to produce mRNA is called transcriptional
region. The upstream (5’) of the transcriptional region is known as promoter. Promoters contain
specific DNA sequences and response elements which provide a secure initial binding site for
RNA polymerase and for other proteins called transcription factors that recruit RNA polymerase.
These transcription factors have specific activator or repressor sequences of corresponding
nucleotides that attach to specific promoters and regulate gene expressions. This position on a

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gene, where transcription begins is called transcription start site. This position on a gene is
indicated by +1. Whereas, enhancers determine what portions of the DNA will be transcribed
into the precursor mRNA (pre-mRNA). The pre-mRNA is then spliced into messenger RNA
(mRNA) which is later translated into protein.

Transcriptional region
-1 +1
5’ 3’

3’ 5’
DNA

5’ 3’
RNA

A1, A2, A3, A4, A4, A6, A7, A8, A9, A10…………………..

Several steps of protein synthesis:

Replication of DNA: DNA is the genetic material. When the cell divides, the daughter cells
receive an identical copy of genetic information from the parent cell.
Replication is a process in which DNA copies itself to produce identical daughter molecules of
DNA. Replication is carried out with high fidelity which is essential for the survival of the
species. Synthesis of a new DNA molecule is a complex process involving a series of steps. The
salient features of replication are described hereunder.
Transcription: Transcription is a process in which ribonucleic acid (RNA) is synthesized from
DNA. The word gene refers to the functional unit of the DNA that can be transcribed. Thus, the
genetic information stored in DNA is expressed through RNA. For this purpose, one of the two
strands of DNA serves as a template (non-coding strand or sense strand) and produces working
copies of RNA molecules. The other DNA strand which does not participate in transcription is
referred to as coding strand or antisense strand (frequently referred to as coding strand since with
the exception of T for U, primary mRNA contains codons with the same base sequence).
Translation: The genetic information stored in DNA is passed on to RNA through transcription.
Biosynthesis of a protein or a polypeptide in a living cell is known as translation. The sequence

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of amino acids in the protein synthesized is determined by the nucleotide base sequence of
mRNA.

DNA
Transcription
RNA
Translation
Protein

Biological action

List of Biotech product:

Serial Generic name Product Company name Indication Appr
No name oval
date
1 Human Insulin Humulin Eli Lily Subcutaneous administration for Oct-
the treatment of diabetes mellitus 1982
type-I and type-II.
2 Someterm Protropin Genetech Multiple scelorosis Oct-
1985
3 Digoxin Digibind Burroughs Indicated for treatment of April-
immune-Fab wellcome potentially life threating digoxin 1986
intoxication
4 Interferon-α-2b Intron A Schering-plough Viral infections and cancers June-
1986
5 Hepatitis-B- Recombivax Merk Vaccinations against infection Julay
vaccine HB caused by Hepatitis-B-virus -1986
6 somatotropin Humatrope Eli Lily Children with growth failure Marc
h-
1987
7 Alteplase Activase Genetech Inadequate assessed in ischemic Nov-
stroke. 1987

253
 8 Heamophilus Hib Titer Praxis Biologics Vaccination against invasive Dec-
B-conjugate disease 1988
vaccine
9 Epoietin-α Epogen Amgen Chronic renal insufficiency June-
1989
10 Interferon-α-n3 AlferonN Interferon sciences Melanoma and essential Oct-
thrombocytes 1989
11 Interferon-γ-Ib Actimmune Genetech Basal cell carcinoma cancer Dec-
1990
12 Filgrastim Neupogen Amgen Neutropenia Feb-
1991
13 Epoitin-α Procrit Ortho biotech Chronic renal failure Feb-
1991
14 Aldesleukin Proleukin Cetus Metastatic malignant melanoma, Jun-
renal carcinoma 1992
15 Darbepoetin-α Aransep Kirin Chronic renal insufficiency Sep-
2001
16 Bosentan Tracleer Genetech Exercise ability hypertension Oct-
2001
17 Anakinra Kineral Amgen Active rheumatoid arthritis Nov-
2001
18 Frovatriptan Frova Elan Migraine attaks in adult Nov-
Succinate pharmaceuticals 2001

Restriction enzymes

Restriction enzymes: A restriction enzyme or restriction endonuclease is an enzyme that

cleaves DNA into fragments at or near specific recognition sites within the molecule known
as restriction sites. Restriction enzymes are commonly classified into four types, which differ in
their structure and whether they cut their DNA substrate at their recognition site, or if the
recognition and cleavage sites are separate from one another. To cut DNA, all restriction
enzymes make two incisions, once through each sugar-phosphate backbone (i.e. each strand) of
the DNA double helix.
Example of restriction endonucleases:
Bam H1. EcoRI. Hind III. Hae II, Bgl II, HpaI, Sal I.
254
 Hybridoma technology

Hybridoma technology: Hybridoma technology is meant for the production of monoclonal

antibodies (MAbs).
Purposes: Antibodies are secreted by a class of blood cells known as B-lymphocytes. These B-
Lymphocytes form a clone of cells called plasma cells. The plasma cells produce proteinaceous
molecules for the specific specific epitope called antibodies. Thus antigen with multiple epitopes
can stimulate a series of B cells, resulting in multiple clones of plasma cells that synthesize
antibodies of different specificities. This is known as polyclonal activation.
Differences between monoclonal and polyclonal antibody:
Polyclonal antibodies Monoclonal antibodies
Derived from many clones of cells. Derived from a single clone of cells.
Contain a mixture of immunoglobulins Contain identical binding sites.
secreted against specific antigen.
Each recognizing different epitopes on any Recognize only one epitope on an antigen.
one antigen.
Inexpensive to produce. Expensive to produce.

Monoclonal antibody-based therapeutics on the market:

Product name Target antigen Therapeutic use Company
(Substance name)
Mabthere/rituxan CD20 surfaceantigen Treatment of Non- Genentech/
(Rituximab) of B lymphocytes Hodgekin’s Hoffmann La-Roche
lymphoma
Herceptin Human epidermal Treatment of Genentech/
(Trastuzumab) growth factor-like metastatic breast Hoffmann La-Roche
receptor 2 (HER2) cancer
overexpressing HER
2 protein

255
Remicade TNF-alfa Treatment of Centocor
(Infliximab) rheumatoid arthritis

ReoPro Platelet surface Prevention of blood Centocor

(Abciximab) receptor GP IIb/IIIa clot

Orthoclone OKT3 T-lymphocyte Reversal of acute Ortho Biotech

(Muromomab) surface antigen CD 3 kidney transplant
rejection

Serology

Serology: The study of antigen-antibody (Ag-Ab) reactions is called serology. The science that
deals with the properties and reactions of serums, especially blood serum.

The most common in-vitro serological tests include:

1. Agglutination
2. Precipitin
3. Complement fixation
4. Lysis by complement
5. Radioimmunoassay (RIA)
6. Enzyme-linked Immunosorbent Assays (ELISA)
7. Opsonization

Antisense technology
 Antisense technology is a nucleic acid based approach to down regulate the expression of
gene with the aim of preventing the inappropriate or over expression derived disease state.
 Various disease states are associated with the inappropriate or overproduction of gene, for
example:
a. The expression of oncogene, leading to cancer.
b. The over expression of cytokines during some disease state, with worsening of disease
symptoms.
c. The over production of angiotensinogen which ultimately results in hypertension.
d. If COX-2 is over expressed in prostate gland there is a chance of prostate cancer.

256
Major classes of antisense agents:
There are three major classes of antisense agents-
1. Antisense oligonucleotides
2. Anti-gene sequence
3. Ribozymes
Use of Antisense technology:
 Antisense oligonucleotides (oligos) are assessed pre-claimed and clinical studies in the
treatment cancer, as well as a variety of viral diseases such as HIV, hepatitis B, Herpes- virus
and papillomavirus infection.
 Antisense technology has also potential application on restenosis, rheumatoid arthritis and
allergic disorder in which blocking of gene expression may have a beneficial effect.

Advantages of Antisense technology:

 Specificity: Antisense oligos display extreme specificity binding with the target mRNA.
 Minimal toxicity: Most trials show that most Antisense technology has few or no side
effects. This is due to the highly specific nature of oligo duplexing and the fact that they are
nature biomolecules.
 Low dose: AS target mRNA is usually present only in nano-molar concentration (nM), the
oligonucleotide required only in low level.
 Easy to synthesis: The ability to manufacture oligos of specified nucleotide sequence is
relatively straight forward using automated synthesizers.

Disadvantage of Antisense technology:

 Sensitivity to nucleuses.
 Very low serum half-lives.
 Poor rate of cellular uptake.
 Orally inactive.

Enzyme immobilization

Enzyme Immobilization: Enzyme Immobilization may be defined as imprisonment of an enzyme

in a distinct phase that allows exchange with but is separated from the bulk phase in which the
substrate, effector or inhibitor molecules are dispersed and monitored.

Advantages of immobilized enzymes:

There are many potential advantages of using immobilized enzymes. They are:
 Reuse:
The same enzyme can be used repeatedly, since they are not lost at the end of a batch.
 Continuous use:
Continuous production system can be designed easily.
257
 Cost effectiveness:
If the enzymes are immobilized, they can be used continuously or repeatedly and hence cost
effectiveness is achieved.
 Less contamination:
Since the immobilized enzyme remains within the polymer matrix, it will not contaminate the
final product.
 Stability:
Immobilization increases the thermal stability of the enzyme. For example, immobilized glucose
isomerase is stable at 650C for almost one year, whereas the pure enzyme is denatured within
few hours at a temperature of 450C.
 Process:
Since the immobilized enzyme have standardized activity, the process control becomes very
easy.
 Enzyme substrate ratio:
It is very high in immobilized enzymes and this increases the cost effectiveness.

Applications of enzyme immobilization:

The enzyme applications are broadly classified into four categories namely-
1. Medical uses.
2. Analytical uses.
3. Manipulative uses.
4. Industrial uses.

Gene therapy

 Genes; those are carried on chromosomes, are the basic physical and functional units of
heredity.
 Gene therapy is a technique for correcting defective genes responsible for disease
development.
 Gene therapy can be described as the intracellular delivery of genetic material to generate a
therapeutic effect by correcting an existing abnormality or providing cells with a new
function.

Delivery approaches of gene therapy:

 Ex vivo delivery (middle).
 In situ delivery (at site).
 In vivo delivery (vein).

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 Immunology

Immunology: Immunology is the study of immune system and very important branch of the
medical and biological sciences. It study about development of vaccines and regulatory
procedure for manipulating the immune response. Immune system protects us from infection
through various lines of difference.
Immunity: Immunity means the capacity of the body to resist infection or to resist the invasion
of foreign particles or micro-organisms that tend to damage our tissues.

Types of Immunity:

Immunity

Natural immunity Acquired immunity

Specie Racial Individual Active Passive

Natural Artificial Natural Artificial

Clinical or Vaccines: Congenital Antiserum
Subclinical- a. Toxoids Colostrum Antitoxin
disease b. Suspensions of γ-globulin
microorganisms

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 Chapter- Eight

Pharmaceutical microbiology

Microbiology: Microbiology is the scientific study of these microorganisms. Microorganisms

are those organisms that are too small to see with the naked eye and include things like bacteria,
fungi, and viruses.
Branches of microbiology:
 Virology
 Mycology
 Bacteriology
 Immunology
 Microbial Ecology
 Biotechnological Microbiology
 Environmental Microbiology
 Food Microbiology
 Forensic Microbiology
 Molecular Biology
Pharmaceutical microbiology: Pharmaceutical microbiology is the part of industrial
microbiology that is responsible for ensuring medications do not contain harmful levels of
microbes- such as bacteria, yeasts and moulds.
Purpose of the section:
Microbiology lab is a part of QC section. In this lab a lot of tests have been done. Basically it
divides in two types:
4. Sterile preparation:
a) Sterility test
b) Bacterial endotoxin test (LAL test)
2. Non- sterile preparation: Limit test for the following pathogenic organism.
a) Escherichia Coli (E. Coli)
b) Salmonella species
c) Staphylococcus aureous
d) Pseudomonas aureginosae

260
 Microbiology

Basic Applied

Disease Disease Environment

By organism By process Industrial
related related ally related

Bacteriology Microbial Food &

metabolism beverage tech
Phycology Immunology Infection
Microbial control Environmental Pharmaceutical
Mycology Epidemiology
genetics microbiology microbiology
Etiology Chemotherapy
Virology Genetic
Microbial
Parasitology Engineering
genetics
Protozoalogy

Bacteria

Bacteria: The word bacteria are the plural of bacterium. Single-celled microorganisms that can
exist either as independent (free-living) organisms or as parasites (dependent on another
organism for life).
There are various diseases that are caused by bacteria such as:
SI No. Name of bacteria Diseases
1. Bacillus anthrax Anthrax
2. Bordetella pertusis Whooping cough
3. Clostridium tetani Tetanus
4. Clostridium botulinum Botulism
5. Mycobacterium tuberculosis Tuberculosis
6. Staphyloccus aureus Wound infection
7. Salmonella typhi Typhoid
8. Vibrocholerac typhi Cholera
9. Neisseria meningitidis Meningitis
10. Yersinia pestis Plugue

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 Types of bacteria

1. Gram positive bacteria

2. Gram negative bacteria
Example of gram-positive bacteria:
1.Bacillus 8.Lactobacillus
2.Nocardia 9.Gardnerella
3.Clostridium 10.Mycobacterium
4.propionibacterium 11.Mycoplasma
5.Actinomyces 12.Staphylococcus
6.Enterococcus 13.Streptoyces
7.Cornyebacterium 14.Sterptococcus

Examples of gram-negative bacteria:

1. Escherichia coli (E.coli) 8. vibrio
2. Helicobcater 9. pseudomona
3. Hemophilus 10. salamonella
4. Neisseria 11. Thiobactr
5. Cyano bacteria 12. Borrelia
6. Klebsiella 13. Burkholderia
7. acetobactor 14. serratia

Differences between Gram positive and gram negative bacteria

Gram-negative Bacteria Gram-positive Bacteria
Gram reaction Can be decolorized to accept counter Retain crystal violet dye and
stain (Safranin or Fuchsine); stain stain dark violet or purple, they
red or pink, they don't retain the remain colored blue or purple
gram stain when washed with with gram stain when washed
absolute alcohol and acetone. with absolute alcohol and
water.
Peptidoglycan layer Thin (single-layered) Thick (multilayered)
Teichoic acids Absent Present in many
Periplasmic space present Absent
Outer membrane Present Absent

262
Lipopolysaccharide High Virtually none
(LPS) content
Lipid and High (due to presence of outer Low (acid-fast bacteria have
lipoprotein content membrane) lipids linked to peptidoglycan)
Flagellar structure 4 rings in basal body 2 rings in basal body
Toxins produced Primarily Endotoxins Primarily Exotoxins
Cell wall The cell wall is 70-120 Å (ångström) The cell wall is 100-120 Å
composition thick; two layered. Lipid content is thick; single layered. Lipid
20-30% (high), Murein content is content of the cell wall is low,
10-20% (low). whereas Murein content is 70-
80% (higher).

Virus

Virus: A virus is a small infectious agent that can replicate only inside the living cells of an
organism. Viruses can infect all types of organisms from animals and plants to bacteria and
archaea.
There are various diseases that are caused by viruses such as:
SI No. Name of the virus Diseases
1. Adenovirus Acute febrile pharyngitis epidemic keratoconjunctivitis
Infantile gastroenteritis.
2. Coxsackie virus Coxsackie infections
4. Hepatitis A virus Acute hepatitis
Hepatitis B virus Chronic hepatitis
Hepatitis C virus
5. HIV AIDS
6. Influenza virus Influenza
7. Mumps virus Mumps
8. Polio virus Poliomyelitis
9. Rabies virus Rabies
10. Rubella virus German measles
Congenital rubella

Differences between bacteria and virus:

Terms Bacteria virus
Living attributes Living organism Opinions after on whether
viruses are a form of life, or
organic structure that is interact
with living organisms.
Number of cells Unicellular No cells; not living

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Ribosomes present Absent
Enzymes yes Yes; in some
Infection Localized systemic
Size Larger Smaller
(1000nm) (20-400)
Beneficial Some bacteria are beneficial Virus are not beneficial Viruses
can be useful in genetic
engineering

Sterilization

Sterilization is the process by which all viable microorganisms including spores are killed or
eliminated.
Five general methods are used for the sterilization of pharmaceutical products:
 Dry heat sterilization
 Moist heat sterilization
 Sterilization by filtration
 Sterilization by ionizing radiation
 Gas sterilization

Dry heat sterilization:

Mechanism of action: Dry heat treatment have two targets: (1) Microorganisms & (2) by –
products produced by them. The aim of sterilization is to destroy the ability of microorganisms to
survive and multiply. Depyrogenation seeks to destroy the chemical activity of the by-products,
pyrogens or endotoxins (synonymous for the sake of simplicity).
Both processes of an oxidation that is almost combustion. However the temperature required to
achieve depyrogenation are distinctly higher than those needed to obtain sterilization. Examples:
Fixed oil, Glycerin.
Advantages:
 It can be used for substances that would be harmed by moisture.
Example: Oily materials and powders.
 It is suitable for assembled equipment, provided sufficient time for penetration is
allowed. Example: all glass syringes.
 It is less damaging to glass and metal equipment than moist heat.
 Some article of porcelain can be sterilized by this method.
Disadvantages:

264
  Most rubbers and plastics cannot be sterilized by this method because they perish.
 The drastic conditions –high temperature, long exposure and very long heating up times
make this method to unsuitable for thermolabile products.
 It is unsuitable for surgical dressings.
 It is a time consuming process and needs high temperature.
Moist heat sterilization:
Microorganisms can be exposed to moist heat by using hot water, boiling water, steam at
atmospheric pressure or steam under pressure (autoclaving). It can kill microorganisms at lower
temperatures and in shorter time then dry heat. For example: All vegetative bacteria are
destroyed at 1 hour at 800C and very few will survive 10 minutes at this temperature. The spores
of clostridium tetani are destroyed by 30 min at 1150C.
Mechanism of action: Moist heat is believed to destroy microorganisms by causing protein
coagulation or denaturation. When heat is applied in the presence of sufficient water, disulphide
bonds and hydrogen bonds between the protein strands of microorganism can be broken and the
strands have sufficient mobility to form new linkages resulting in the denaturing of the protein,
which if it is part of an enzyme will render it inactive.
Advantages:
 It is suitable for surgical dressing
 Most medicaments, rubbers and plastics are sterilized by this method.
 It can kill microorganisms at lower temperature and in shorter time.
 PVC can be sterilized by this method.
 The apparatus is inexpensive and simple.
Disadvantages:
 It cannot be used for substances that would be harmed by moisture.
Example: Oily materials and powders.
 It is more damaging to glass and metal equipment then dry heat.
 It cannot be used for injections and articles, such as some plastics, that deteriorate at
1150c.
Sterilization by filtration:
Filtration through a bacteria proof filter is a suitable method for sterilization of injections
containing thermolabile medicaments. Generally thermolabile medicaments would suffer
damage if subjected to heat sterilization. The process involve four stages:

 Filtration of the solution through a bacteria proof filter.

 Aseptic distribution of the filtrated solution into previously sterilized containers.
 Aseptic closers of the containers.
 Testing of sample of sterility

265
Advantages:
 No heat is used, thus ideal for thermolabile solutions.
 Remove all bacteria and fungi and often clarifies the solutions.
 Useful process for sterilization of large volume solution.
 Useful for eye drops as dropper bottle do not withstand heating processes well.
Disadvantages:
 Aseptic technique is required. Thus highly trained staff and sterile equipment and
facilities are required.
 Viruses, filtrated forms of bacteria and bacterial products such as toxins and pyrogens are
not removed or destroyed.
 Filter may break down either suddenly or gradually is use.
 Filtration unit may leak and permit entry of non-sterile air.

Culture Media

A growth medium or culture medium: A growth medium or culture medium is a liquid or gel
designed to support the growth of microorganisms or cells. There are different types of media for
growing different types of cells.
Need for Culture media:
 Bacteria: mixed population in nature.
 By appropriate procedures they have to be grown separately (isolated) on culture media and
obtained as pure culture for study.
 Medium → Nutrients → support growth.

Culture medium

Liquid medium Solid medium

Liquid medium:
 Diffused growth.
 No characteristics for identification.
 Difficult to isolate.
 Earliest liquid medium: urine or meat broth used by Louis Pasteur.

266
Solid medium:
 Distinct colony morphology.
 Characteristics → easy to identify.
 Colony – macroscopically visible collection of millions of bacteria originating from a
single bacterial cell.
 Earliest solid medium: Cooked cut potato by Robert Koc.
 Gelatin:
– Not satisfactory
– Liquefy at 24°C
Agar:
 Universally used for preparing solid medium.
 Obtained from seaweed: Gelidium.
 No nutritive value.
 Not affected by the growth of the bacteria.
 Melts at 98°C & sets at 42°C.
 2% agar is employed in solid medium.

Types of media:
1. Nutrient media: An undefined medium (also known as a basal or complex medium) is a
medium that contains: a carbon source such as glucose for bacterial growth after various salts
needed for bacterial growth a source of amino acids and nitrogen (e.g. beef, yeast extract).

2. Different media: Some sort of indicator, typically a dye is added, that allows for the
differentiation of particular chemical reaction occurring during growth.

3. Minimal media: Minimal media are those that contain the minimum nutrient possible for
colony growth, generally without the presence of amino acids, and are often used by
microbiologists and geneticists to grow “wild type” microorganisms. Minimal media can also
be used to select for against recombinants or exconjugants.

4. Selective media: Blood agar plates are often used to diagnose infection. On the right is
positive Streptococcus culture; on the left a positive staphylococcus culture. Selective media
are used for the growth of only select microorganisms.

5. Transport media: These are used for the temporary storage of specimens being transported
to the laboratory for cultivation. Such media ideally maintain the viability of all organisms in
the specimen without altering their concentration. Transport media typically contain only
buffer and salt. The lack of carbon, nitrogen, and organic growth factors prevents microbial

267
 multiplication. Transport media used in the isolation of anaerobes must be free of molecular
oxygen.

6. Enriched media: Enriched media contain the nutrients required to support the growth of a
wide variety of organisms, including some of the more fastidious ones. They are commonly
used to harvest as many different types of microbes as are present in the specimen. Blood
agar is an enriched medium in which nutritionally rich whole blood supplements the basic
nutrients. Chocolate agar is enriched with heat treated blood (40-50°C), which turns brown
and gives the medium the color for which it is named.

Fungi

Fungi: Fungus is a general term used to describe all yeasts and moulds, whereas a mould is the
filamentous fungus exhibiting a mycelial form of growth. Fungal cell wall are composed
predominantly of polysaccharide, is the most cases this chitin mixed with cellulose, glucan and
mannan.
Fungal morphology:
The fungi can be divided into five broad groups on the basis of their morphology.
a) Yeasts: These are spherical or ovoid unicellular bodies2-4/xm in diameter which typically
reproduce by budding. In liquid cultures and on agar they behave very much like bacteria.
Examples include: Saccharomyces cerevisiae, strains of which are used in backing and in the
production of beers and wines.
b) Yeast-like fungi: These organisms normally behave like a typical budding yeasts but under
certain circumstances the buds do not separate and become elongated. The resulting structure
resembles a filament and is called a pseudomycelium.
c) Dimorphic fungi: These grow as yeasts or as filaments depending upon the cultural
conditions. At 22℃, either in the soil or in culture media, filamentous mycelial forms and
reproductive spores are produced, whereas at 37℃ in the body the microorganism assume a
yeast-like appearance. Histoplasma capsulatum is an important pathogen that gives rise to
respiratory illness.
d) Filamentous fungi: This group comprises those multicellular moulds that grow in the form
of long, slender filaments 2-10 yum diameter called hyphae. The branching hyphae, which
constitute the vegetative or somatic structure of the mould, intertwine and gradually spread
over the entire surface of the available substrate, extracting nutrients and forming a dense
mat or mycelium.
e) Mushrooms and toadstools: This group is characterized by the production of large
reproductive fruiting bodies of complex structure. They also possess elaborate propagation
mechanisms. Some of these are edible and are used in cooking, but others such as Amanita
phalloides (Death Angel) produce potent mycotoxins that may result in death if eaten.

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 MIC

Minimum inhibitory concentration determinations (MICs):

The MIC is the lowest concentration of an antimicrobial chemical found to inhibit the growth of
particular test organism. It is therefore a fundamental measure of the intrinsic antimicrobial
activity (potency) of a chemical, which may be an antiseptic, disinfectant, preservative or
antibiotic. MIC determination are applied to chemicals in pure state, i.e. They are particularly
relevant to raw materials rather than to the final formulated medicines; the later are usually
subject to preservative efficacy (challenge) tests to assess their antimicrobial activity.

Staining

Staining: Coloring the microorganisms with a dye that emphasis certain structures is called
staining.

Simple stain Differential stain

 Staining with one dye.  Gram stain.
 Mordant may be used to hold  Acid-fast stain.
the stain or to coat the
specimen to enlarge it.

Gram stain Acid-fast stain

 Gram +ve and gram –ve. Stained waxy cell wall is not decolorized
 Gram +ve bacteria are prone by acid-alcohol
to penicillin and detergents.
 Gram –ve are more resistant  Mycobacterium.
to antibiotics.  Nocardia.

Special stain
Distinguish special parts of cells
 Capsule.
 Endospore (Malachite green
and safranin).
 Flagella (carbolfuchsin simple
stain).

269
 Contamination

Sources and incidence of contamination:

Microorganisms form an integral part of our environment. They are present in the air that we
breathe, the food that we eat and the water that we drink. Some microorganisms indigenous to
the body are present in considerable numbers: they are constitute up to one-third of the dry
weight of faeces. In this situation it is apparent that both raw materials and final medicines will
contain microorganisms unless specific measures is a skilled and expensive procedure
demanding sophisticated equipment, skilled personnel and a controlled working environment. To
produce all medicines to such a standard would require clear argument to justify the considerable
costs involved and the consequent expense to consumers.
Factors to be considerable are:
The sources and incidence of microorganisms in drug and medical preparations, the
consequences of such contamination both for the stability of medicines and for the health of the
patient and arising from these and types of microorganism that might be tolerated. A major
potential sources of microbial contamination is that represented by the personnel preparation
medicines and the patient using them.

Cross- contamination

Cross-contamination: Contamination of a starting material, intermediate product or finished

product with another starting material or product during production.
Cross-contamination should be avoided by appropriate technical or organizational measure for
example:
a) Production is segregated areas: Which may be required for products such as penicillin, live
vaccines, live bacterial preparation and certain other biological or by campaign (separated in
time) followed by appropriate cleaning.
b) Providing appropriate airlock, pressure differentials and extraction.
c) Minimize the risk of contamination caused by recirculation or re-entry of untreated or
insufficient treated air.
d) Wearing protective clothing in areas where products with special risk of cross-contamination
are produced.
e) Using cleaning and decontamination procedures of known effectiveness as infective cleaning
of equipment is a common source of cross-contamination.
f) Using a closed system of production.
g) Testing for residues.
h) Using cleanliness status labels on equipment.

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 Chapter-Nine

Biopharmaceutics and Pharmacokinetics

Biopharmaceutics: Branch of pharmaceutics (pharmaceutical sciences) dealing with the study

of relationship of physicochemical properties of drugs and drug products with their
pharmacological and therapeutic activities in man and animals.

Physicochemical properties Pharmacological and therapeutic

of drugs and drug products activity of drug and drug products

Biopharmaceutics is the
study of relationship
between these two areas

According to the biopharmaceuticals classification system drug substances are classified as

follows:
 Class 1-High permeability, High solubility
Those compounds are well absorbed and their absorption rate is usually higher than
excretion.
Example: Metoprolol.
 Class 2- High permeability, Low solubility
The bioavailability of those products is limited by their solvation rate. A correlation
between the in vivo bioavailability and the in vitro solvation can be found.
Example: Glibenclamide, Bicalutamide, ezetimibe.
 Class 3- Low permeability, High solubility
The absorption is limited by the permeation rate but the drug is solvated very fast. If the
formulation does not change the permeability or solvated very fast. If the formulation
does not change the permeability or gastro-intestinal duration, then class 1 criteria can be
applied.
Example: cimetidine
 Class 4- Low permeability, Low solubility
Those compounds have a poor bioavailability. Usually they are not well absorbed over
the intestinal mucosa and a high variability is expected.
Example: hydrochlorothiazide.

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 ADME

ADME is an acronym in pharmacokinetics and pharmacology for absorption, distribution,

metabolism and excretion and describes the disposition of a pharmaceutical compound within an
organism. The four criteria all influence the drug levels and kinetics of drug exposure to the
tissues and hence influence the performance and pharmacological activity of the compound as a
drug.
Absorption: For a compound to reach a tissue, it usually must be taken in to the bloodstream-
often via mucous surfaces like the digestive tract (intestinal absorption) – before being taken up
by the target cells. Factors such as poor compound solubility, gastric emptying time, intestinal
transit time, chemical instability in the stomach, and inability to permeate the intestinal wall can
all reduce the extent to which a drug is absorbed after oral administration.
Distribution: Distribution is defined as the reversible transfer of a drug between one component
to another. Some factors affecting drug distribution include regional blood flow rates, molecular
size, polarity and binding to serum proteins, forming a complex. Distribution can be a serious
problem at some natural barriers like the blood-brain barrier.
Metabolism: Compounds begin to break down as soon as they enter the body. The majority of
small-molecule drug metabolism is carried out in the liver by redox enzymes, termed cytochrome
p450 enzymes. As metabolism occurs, the initial (parent) compound is converted to new
compounds called metabolites. When metabolites are pharmacologically inert, metabolism
deactivates the administered dose of parent drug and this usually reduces the effect on the body.
Excretion: Compounds and their metabolites need to be removed from the body via excretion,
usually through the kidneys or in the feces. Unless excretion affect normal metabolism, there are
three main sites where drug excretion occurs. The kidney is the most important site and it is
where products are excreted through urine. Biliary excretion or fecal excretion is the process that
initiates in the liver and passes through to the gut until the products are finally excreted along
with waste products or feces. The last main method of excretion is through the lungs e.g.
anesthetic gases.

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 Bioavailability

Bioavailability: Bioavailability refers to rate and extent of drug appearing in blood. Thus, the
rate and extent of absorption of drugs is known as Bioavailability.

Bioavailability Pharmacological / therapeutic response

There is a definite
relationship between
these two parameters

For example, if 100mg of a drug is administered orally and 70 mg of this drug is absorbed
unchanged, the bioavailability is 70%.
Bioavailability is of two types- (I) Relative bioavailability (II) Absolute bioavailability
Relative bioavailability: Relative bioavailability measures the bioavailability of a formulation
of certain drug when compared with another formulation of the same drug, usually an established
standard, though administration via a different route.

Fastest
Aqueous solution
Bioavailability
Emulsion
Suspension
Soft gelatin capsule
Hard gelatin capsule
Tablet
Coated tablet
Slowest Enteric coated tablet
Bioavailability Sustained release products

Figure: Relative bioavailability from oral dosage forms

Absolute bioavailability: Absolute bioavailability is the amount of drug from a formulation that
reaches the systemic circulation relative to an intravenous (IV) dose. The IV dose is assumed to
be 100% bioavailable, since you are injecting the drug directly into the systemic circulation.
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Pharmacokinetics refers to the studies of rates of drug absorption, distribution, metabolism and
excretion (ADME). It determines change of ADME processes with time.
Pharmacodynamics refers to the relationship between the drug concentration at the site of
action (receptor) and pharmacological response, including biochemical and physiological effects
that influence the interaction of drug with the receptors. Thus, it represents the mechanism of
drug actions and their pharmacological effects.

First pass metabolism/ Effects

First pass effects: The first pass effect also known as first-pass metabolism is a phenomenon
of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the
systemic circulation. It is the fraction of drug lost during the process of absorption which is
generally related to the liver and gut wall. Notable drugs that experience a significant first-pass
effectare imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, pethidine, ci
metidine, lidocaine and nitroglycerin. After a drug is swallowed, it is absorbed by the digestive
system and enters the hepatic portal system. It is carried through the portal vein into
the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to
such an extent that only a small amount of active drug emerges from the liver to the rest of
the circulatory system. This first pass through the liver thus greatly reduces the bioavailability of
the drug.
The four primary systems that affect the first pass effect of a drug are the enzymes of
the gastrointestinal lumen, gut wall enzymes, bacterial enzymes, and hepatic enzymes.
In drug design, drug candidates may have good drug likeness but fail on first-pass metabolism
because it is biochemically selective.

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Alternative routes of administration like suppository, intravenous, intramuscular, inhalational
aerosol, transdermal and sublingual avoid the first-pass effect because they allow drugs to be
absorbed directly into the systemic circulation.

Half-life

It is the time in which the concentration of drug declines by one half.

Types of half-life:
a) Plasma half-life: It is the time taken for the plasma concentrations of drugs in the body
to be reduced to half of its original volume.
b) Elimination half-life: The time in which the total amount of drug in the body after
equilibrium of plasma with other compartments is halved.
c) Biological effective half-life: The time in which the pharmacological effect of the drug
and of any active metabolites has declined of one half.

Creatinine and Creatinine Clearance

Creatinine is a waste product that is produced continuously during normal muscle breakdown. The
kidneys filter creatinine from the blood into the urine and reabsorb almost none of it. The amount of
blood the kidneys can make creatinine-free each minute is called the creatinine clearance. Creatinine
clearance in a healthy young person is about 125 milliliters per minute -- meaning each minute, that
person's kidneys clear 125 mL of blood free of creatinine. The GFR can vary depending on age, sex,
and size. Generally, the creatinine clearance is a good estimation of the glomerular filtration rate.

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 Chemical reactions

Classification of chemical reactions according to their reaction kinetics.

Chemical reactions can be classified based on their reaction kinetics. The general reaction form
is:
𝑎𝐴 + 𝑏𝐵 → 𝑐𝐶 + 𝑑𝐷
Reactions are categorized as zero-order reactions, first order, and second order or, mixed order
(higher order) reactions.
1. Zero order reactions: Zero order reaction (order=0) have a constant rate. This rate is
independent of the concentration of the reactants. The rate law is: rate= k, with k having the
units of M/sec.
2. First order reactions: A first order reaction (order =1) has a rate proportional to the
concentration of one of the reactants. A common example of a first-order reaction is the
phenomenon of radioactive decay. The rate law is: rate = k [A] (or B instead of A) with
having the units of sec-1.
3. Second order reactions: A second order reaction (order = 2) has a rate proportional to the
concentration of the square of a single reactant or the product of the concentration of two
reactants: rate = k[A]2 (or substitute B for A or k multiplied by the concentration of A times
the concentration of B), with the units of the rate constant M-1 sec -1
4. Mixed order or higher-order reactions: Mixed-order reactions have a fractional order for
their rate: e.g. rate = k[A]1/3

Volume of distribution

Volume of Distribution (VD): The distribution volume may be defined as the volume of fluid in
which the drug appears to distribute with a concentration equal to that in plasma.
The VD of a drug represents the degree to which a drug is distributed in body tissue rather than
the plasma. VD is directly correlated with the amount of drug distributed into tissue; a higher
VD indicates a greater amount of tissue distribution. A VD greater than the total volume of body
water (approximately 42 liters in humans) is possible and would indicate that the drug is highly
distributed into tissue.
In rough terms, drugs with a high lipid solubility (non-polar drugs), low rates of ionization, or
low plasma binding capabilities have higher volumes of distribution than drugs which are more
polar, more highly ionized or exhibit high plasma binding in the body's environment. Volume of
distribution may be increased by renal failure (due to fluid retention) and liver failure (due to
altered body fluid and plasma protein binding). Conversely it may be decreased in dehydration.

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Equations: The volume of distribution is given by the following equation:
Total amount of drug in the body
VD =
Drug blood plasma concentration

Plasma protein binding

Plasma protein binding: A drug’s efficacy may be affected by the degree to which it binds to
the proteins within blood plasma. The less bound a drug is, the more efficiently it can traverse
cell membrane or diffuse. Common blood proteins to which drugs bind are human serum
albumin, lipoprotein, glycoprotein, and α, β, and γ globulins.
A drug in blood exits in two forms: bound and unbound. Depending on a specific drugs affinity
for plasma proteins, with the remainder being unbound. If the protein binding is reversible, then
a chemical equilibrium will exist between the bound and unbound states, such that: protein +
drug = protein-drug complex.

Cmax& Tmax
Cmax: It is a term used in pharmacokinetics refers to the maximum concentration that a drug
achieves in tested area after the drug has been administrated and prior to the administration of a
second dose. Cmax is the opposite of Cmin, which is the minimum concentration that a drug
achieves after dosing.
Tmax: The amount of time that a drug is present at the maximum concentration in serum.

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 Chapter-Ten

Pharmaceutical regulatory affairs

Code of Ethics

Code of Ethics for Pharmacists:

Pharmacists are health professionals who assist individuals in making the best use of
medications. This Code prepared and supported by pharmacists is intended to state publicly the
principles that form the fundamental basis of the roles and responsibilities of pharmacists. These
principles, based on moral obligations and virtues, are established to guide pharmacists in
relationships with patients, health professionals, and society.

I. A pharmacist respects the covenantal relationship between the patient and pharmacist.

Considering the patient-pharmacist relationship as a covenant means that a pharmacist has moral
obligations in response to the gift of trust received from society. In return for this gift, a
pharmacist promises to help individuals achieve optimum benefit from their medications, to be
committed to their welfare, and to maintain their trust.

II. A pharmacist promotes the good of every patient in a caring, compassionate, and
confidential manner.

A pharmacist places concern for the well-being of the patient at the center of professional
practice. In doing so, a pharmacist considers needs stated by the patient as well as those defined
by health science. A pharmacist is dedicated to protecting the dignity of the patient. With a
caring attitude and a compassionate spirit, a pharmacist focuses on serving the patient in a
private and confidential manner.

III. A pharmacist respects the autonomy and dignity of each patient.

A pharmacist promotes the right of self-determination and recognizes individual self-worth by

encouraging patients to participate in decisions about their health. A pharmacist communicates
with patients in terms that are understandable. In all cases, a pharmacist respects personal and
cultural differences among patients.

IV. A pharmacist acts with honesty and integrity in professional relationships.

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A pharmacist has a duty to tell the truth and to act with conviction of conscience. A pharmacist
avoids discriminatory practices, behavior or work conditions that impair professional judgment,
and actions that compromise dedication to the best interests of patients.

V. A pharmacist maintains professional competence.

A pharmacist has a duty to maintain knowledge and abilities as new medications, devices, and
technologies become available and as health information advances.

VI. A pharmacist respects the values and abilities of colleagues and other health
professionals.

When appropriate, a pharmacist asks for the consultation of colleagues or other health
professionals or refers the patient. A pharmacist acknowledges that colleagues and other health
professionals may differ in the beliefs and values they apply to the care of the patient.

VII. A pharmacist serves individual, community, and societal needs.

The primary obligation of a pharmacist is to individual patients. However, the obligations of a

pharmacist may at times extend beyond the individual to the community and society. In these
situations, the pharmacist recognizes the responsibilities that accompany these obligations and
acts accordingly.

VIII. A pharmacist seeks justice in the distribution of health resources.

When health resources are allocated, a pharmacist is fair and equitable, balancing the needs of
patients and society.

The pharmacy ordinance

Act: An act is a formal transduction of legislative or other deliberative body.

Rule: A generalized statement that describe what is true in most or all cases.
Law: Law literally means a rule of action established by authority, a statute, the rule of a
community or state etc. It is a pillar of human society and is necessary for each and every phase
of life. Law and human are in separable. It is an authoritative instrument which is always
promulgated under government authority caring at its back a force of punishment.
Ordinance: The term ordinance means a rule that is trained or established by the authority. It is
an authoritative regulation, decree, law, or practice.
Ethics: Ethics is the branch of philosophy and science of moral principle. It includes oaths of
ethical conducts for men in all walks of life and professions relevant to their special needs .All
written or unwritten principles which are expected in any professions as the basis of proper

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behavior constitute the ethics of profession. Law is enforced by the state and ethics is only moral
being.

Chronological Evolution of Prevailing Drug Regulations in Bangladesh

 Poison Act 1919

 Dangerous Drugs Act 1930
 Drug Act 1940
 Bengal Drug Rules 1946
 Dangerous Drugs Act 1951
 Poison Act 1952
 Unani Ayurvedic and Homeopathic Practitioners Act 1965
 Unani Ayurvedic and Homeopathic Systems of Medicines 1965
 Bengal Drug Rules (Amendment)1970
 Pharmacy Council Ordinance 1976
 Drug (Control)Ordinance 1982 (National Drug Policy1982)
 Unani Ayurvedic Practitioners Ordinance1983
 Homeopathic Practitioners Ordinance1983
 Narcotic (Control)Act 1990
 Drug (Control) (Amendment) Rules 1997
 Drug (Control) (Amendment) Act Rules 2005(National Drug Policy2005)

The drugs (control) ordinance, 1982, Bangladesh

This Ordinance was made and promulgated by the Ministry of Law and Land Reforms (Law and
Parliamentary Affairs Division) of the People's Republic of Bangladesh on 11th June, 1982 as
Ordinance No VIII of 1982. The provisions of this Ordinance are additional to, and not
derogatory of, the Drugs Act, 1940. Through this Ordinance, the government has constituted
different committees; some of these are as follow:

(i) A Drug Control Committee consisting of a Chairman and a varied number of members
appointed by the government from time to time to perform such functions as are specified
in the Ordinance, and
(ii) A National Drug Advisory Council consisting of a Chairman and such other members as
the government may appoint from time to time.

Under this Ordinance following are maintained strictly:

(i) No medicine of any kind can be manufactured for sale or be imported, distributed or
sold unless it is registered with the licensing authority;
(ii) No drug or pharmaceutical raw material can be imported into the country except with
the prior approval of the licensing authority;

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(iii) The licensing authority cannot register a medicine unless such registration is
recommended by the Drug Control Committee;
(iv) The licensing authority may cancel the registration of any medicine if such
cancellation is recommended by the Drug Control Committee on finding that such a
medicine is not safe, efficacious or useful;
(v) The licensing authority is also empowered to temporarily suspend the registration of
any medicine if it is satisfied that such a medicine is substandard;
(vi) The government may, by notification in the official gazette, fix the maximum price at
which any medicine may be sold and at which any pharmaceutical raw material may
be imported or sold;
(vii) No person is allowed to manufacture any drug except under the personal supervision
of a pharmacist registered in Register 'A' of the Pharmacy Council of Bangladesh;
(viii) No person, being a retailer, is allowed to sell any drug without the personal
supervision of a pharmacist registered in any Register of the Pharmacy Council of
Bangladesh; and
(ix) The government may, by notification in the official Gazette, establish Drug Courts as
and when it considers necessary.

DGDA

The Directorate General of Drug Administration (DGDA) under the Ministry of Health &
Family Welfare, Government of the People's Republic of Bangladesh, is the Drug Regulatory
Authority of the country. This DGDA supervises and implements all prevailing Drug
Regulations in the country and regulates all activities related to import, procurement of raw and
packing materials, production and import of finished drugs, export, sales, pricing, etc. of all
kinds of medicines including those of Ayurvedic, Unani, Herbal and Homoeopathic systems. At
present, there are 47 district offices under the DGDA in the country. All the officers of the
DGDA function as "Drug Inspector" in pursuant to the Drug Laws and assist the Licensing
Authority to discharging his responsibilities properly. Besides, a number of Committees, such as
Drug Control Committee (DCC), Standing Committee for imports of raw materials and finished
drugs, Pricing Committee and a number of other relevant Committees, which comprise of
experts of different fields, are there to advice Licensing Authority and recommend him about the
matters related to drugs and medicines.

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 ICH

“International Conference on Harmonisation of Technical Requirements for Registration of

Pharmaceuticals for Human Use’’ (ICH)
A Unique Approach:
International Conference on Harmonisation (ICH) was created in 1990. Agreement between the
EU, Japan and the USA to harmonize different regional requirements for registration of
pharmaceutical drug products. Unique because joint effort by regulators and associated
pharmaceutical industry trade associations.
Mission:
To make recommendations towards achieving greater harmonization in the interpretation and
application of technical guidelines and requirements for pharmaceutical product registration,
thereby reducing duplicating of testing carries out during the research & development of new
human medicines.
Purpose of ICH:
 Harmonisation of technical requirements
 Ensure safety, efficacy and quality of medicines
 Prevent duplication of clinical trials in humans
 Minimize the use of animal testing without compromising safety and effectiveness

ICH Guidelines include – Q S E M

Quality (Q1-Q11)
– Chemical & Pharmaceutical QA
Safety (S1-S10, M3)
– Dealing with in vitro & in vivo preclinical testing
Efficacy (E1-E16, Except E13)
– Clinical studies in human beings
Multidisciplinary (M1-M8)
– Terminology, electronic standards, common documents

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Q S E M under ICH guideline.

Quality Safety
Q1-Stability S1-Carcinogenicity Studies
Q2-Analytical Validation S2-Genotoxicity Studies
Q3-Impurities S3-Toxicokinetics and Pharmacokinetics
Q4-Pharmacopoeias S4-Toxicity Testing
Q5-Quality of Biotechnological S5-Reproductive Toxicology
Products
S6-Biotechnological Products
Q6-Specifications
S7-Pharmacology Studies
Q7-Good Manufacturing Practice
S8-Immunotoxicology Studies
Q8-Pharmaceutical Development
S9-Nonclinical evaluation for anticancer
Q9-Quality Risk Management pharmaceuticals
Q10-Pharmaceutical Quality System S10-Photosafety Evaluation

Efficacy Multidisciplinary
E1&E2-Clinical Safety M1-MedDRA Terminology
E3-Clinical Study Reports M2-Electronic Standards
E4-Dose-Response Studies M3-Non-clinical Safety Studies
E5-Ethnic Factors M4-CTD
E6-Good Clinical Practice M5-Data elements & Standards for Drug
dictionaries
E7, E8, E9, E10, E11-Clinical Trials
M6-Gene Therapy
E12-Guidelines for Clinical
Evaluation by Therapeutic Category M7-Genotoxic Impurities
E14-Clinical Evaluation M8-eCTD
E15&E16-Pharmacogenomics

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 MHRA
MHRA: The Medicines and Healthcare products Regulatory Agency (MHRA) is a UK
government agency which is responsible for ensuring that medicines and medical devices work
and are acceptably safe. The medicines and Healthcare products Regulatory Agency was formed
in 2003 with the merger of the Medicines Control Agency (MCA) and the Medical Devices
Agency (MDA). In April 2013, it merged with the National Institute for Biological Standards
and Control (NIBSC) and was rebranded, with the MHRA identity being used for the parent
organization and one of the centres within the group. It is an executive agency of the Department
of Health.

Roles of MHRA:
a) Operate post-marketing surveillance for reporting, investigating and monitoring of adverse
drug reactions to medicines and incidents with medical devices.
b) Assessment and authorization of medicinal products for sale and supply in UK.
c) Oversee the Notified Bodies that ensure medical device manufacturers comply with
regulatory requirements before putting devices on the market.
d) Operate a quality surveillance system to sample and test medicines to address quality defects
and to monitor the safety and quality of unlicensed products.
e) Investigate internet sales and potential counterfeiting of medicines, and prosecute where
necessary.
f) Regulate clinical trials of medicines and medical devices.
g) Monitor and ensure compliance with statutory obligations relating to medicines and medical
devices.
h) Promote safe use of medicines and devices.
i) Mange the Clinical Practice Research Data link and the British pharmacopoeia.

Dossier

Pharmaceutical dossier: The word “Dossier” has its English meaning as - a collection or file of
documents on the same subject, especially a file containing detailed information about a person
or a topic. Any preparation for human use that is intended to modify or explore physiological
systems or pathological states for the benefit of the recipient is called as “pharmaceutical product
for human use”. Process of reviewing and assessing the dossier of a pharmaceutical product
containing its detailed data (administrative, chemistry, pre-clinical and clinical) and the
permission granted by the Regulatory Agencies of a country with a view to support its marketing
/ approval in a country is called as the “Marketing Approval or the “Registration” “Marketing
Authorization” or the “Product Licensing”.
The pharmaceutical dossier includes:
1. The company information in which that product was manufactured.
2. The master formula of the product.
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 3. The manufacturing procedure and the requirements list used in the production
4. The stability data
5. Specifications used in testing the final product.
6. Other documents.
The list of other documents may vary according to the country regulatory authority guidelines.

CTD and ACTD

The Common Technical Document (CTD): Is a set of specification for application dossier for
the registration of Medicines and designed to be used across Europe, Japan and the United
States. It is an internationally agreed format for the preparation of applications regarding new
drugs intended to be submitted to regional regulatory authorities in participating countries. It was
developed by the European Medicines Agency (EMA, Europe), the Food and Drug
Administration (FDA, US) and the Ministry of Health, Labour and Welfare (Japan). The CTD is
maintained by the International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH).

The Common Technical Document is divided into five modules:

1. Administrative and prescribing information

2. Overview and summary of modules 3 to 5
3. Quality (pharmaceutical documentation)
4. Preclinical (Pharmacology/Toxicology)
5. Clinical – efficacy (Clinical Trials)

This ASEAN Common Technical Dossier (ACTD): Is a guideline of the agreed upon common
format for the preparation of a well-structured Common Technical Dossier (CTD) applications
that will be submitted to ASEAN regulatory authorities for the registration of pharmaceuticals
for human use. This guideline describes a CTD format that will significantly reduce the time and
resources needed to compile applications for registration and in the future, will ease the
preparation of electronic documental submissions. Regulatory reviews and communication with
the applicant will be facilitated by a standard document of common elements.

GATT / TRIPS CHRONOLOGY

1945: Uruguay Round Talks of Developed Countries Began.

1947: General Agreement on Trade and Tariffs (GATT) Signed by 23 Developed Countries.
1986: Trade Liberalization Talks under GATT again initiated.
1994: World Trade Organization (WTO) Formed to implement GATT

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It also included:
– Agriculture
– Service
– Investment Measures
– Protection of Intellectual Property
1994: WTO framed another agreement on protection of intellectual property, which is called –
Trade Related Aspects of Intellectual Property Rights (TRIPS).All the Components of
GATT and TRIPS declared to be effective from 2005.World Intellectual Property
Organization (WIPO) formed under WTO to deal with patents.

TRIPS

Trade Related Aspects on Intellectual Property (TRIPS): Intellectual property rights were
brought into the GATT/ WTO framework for the first time in the Uruguay Round. The
agreement on TRIPS was entered into force on 1st January 1995, along with the other WTO
agreements.
The TRIPS agreement contains relatively high minimum standards for IP protection for any
invention, whether a product or a process, while allowing certain exceptions and lasts for at least
20 years from the date of patent application was filed.
Impact of TRIPS on Bangladesh Pharmaceutical Industry:
Impact of WTO TRIPS on Bangladesh Pharmaceutical Industry can be twofold: Up to
31.12.2015 (when patent protection is not mandatory) and after 31.12.2015 (when giving patent
protection will be mandatory). Up to 1st January 2016, TRIPS provides Bangladesh and other
LDCs the transition period to manufacture and export patented drugs. This has come as a
blessing in disguise for Bangladesh as Bangladesh is the only country among LDCs which has a
strong pharmaceuticals manufacturing base. During this time, Bangladesh as a LDC would be
able to expert medicines without giving patent protection.
To avail the opportunities under TRIPS, a number of pharmaceutical companies including
Square, Incepta, Beximco, Acme, Opsonin, Orion etc, invested a substantial amount of money to
enhance their production capacity.
Bangladesh is graded as a developing country before 2016, all the WTO TRIPS flexibilities
allowed for LDCs will be lost for Bangladesh. After January 1, 2016 the situation for Bangladesh
pharmaceutical industries would change significantly after the expiry of the transition period on
01.01. 2016. From that date, the country must provide patent protection to pharmaceutical
products as per TRIPS agreement. Inevitably this will mean that prices will increase, generic
drug producers will be hurt. Moreover, TRIPS rules will limit export market for Bangladesh
pharmaceutical products. Bangladesh’s pharmaceutical products export will be confined to LDC
countries, countries that issued CL and those markets where patent protection does not exist.

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 Chapter- Eleven

Pharmaceutical marketing

Market

A Market represents the aggregate demand of the buyers and potential buyers for a product or
service over a specific period of time.

Marketing

 Marketing is a human activity directed at satisfying needs and wants through exchange
process.
 Marketing is creating and retaining customer by creating value!!!!
 Marketing is the process of creating demand and satisfy customer needs
Philip Kotler, the eminent writer, defines modern marketing as, “Marketing is social and
managerial process by which individuals and groups obtains what they needs and wants
through creating and exchanging product and value with others.’’
PHILIP KOTLER DEFINES MARKETING AS CC DV TP!!!!!!!
 CREATE
 COMMUNICATE
 DELIVER
 VALUE
 TARGET MARKET
 PROFIT

Marketing management

Marketing Management is the analysis, planning, implementation, and control of programs

designed to create, build, and maintain beneficial exchanges with target markets in order to
achieve organizational objectives.

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Core Marketing Concepts:
Needs are the basic human requirements.
Example:
 A person needs a transport.
 A patients is suffering from fever, he needs to recover.
Needs become wants when they are directed to specific objective that might satisfy the need;
Example:
 He may want a Honda Civic car.
 Patient wants to recover quickly and visit doctor.
Demands are wants for specific products backed by an ability to pay;
Example:
 Many people want a Mercedes; but only a few are willing and able to buy one.
 Doctor prescribe a medicine based on the patients disease.

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 Marketing process

Marketing Mix – 4Ps

The marketing mix elements that make up an organization’s marketing program:

1. Product
2. Promotion
3. Price
4. Place

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 The marketing communications mix

Various categories of promotional tools available to marketers—all contributing to the role of the
whole marketing communications mix—a combination of
 Advertising
 Direct-response promotion
 Sales promotion
 Publicity
 Public relations
 Personal selling

Advertising

Marketing managers must decide

 Who is their target audience
 What kind of advertising to use
 How to reach customers (via which types of media)
 What to say to them (the copy strategy)
 Who will do the work (the company’s own advertising department or an outside agency)
The importance of advertising:
 Involves a huge amount of money
 Work is done by relatively few people
 Major expense is for media time/space
 Companies spend only a small percentage of sales on advertising
Setting advertising objectives:
 Help introduce new products to specific target markets
 Help position the firm's brand or marketing mix by informing and persuading target
customers or intermediaries about its benefits
 Help obtain desirable outlets (distribution)
 Provide ongoing contact with target customers
 Prepare the way for the personal selling effort
 Get immediate buying action
 Help buyers confirm purchasing decisions

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 Awareness Interest Evaluation and
Decision
trial
Teaser campaigns Informative or
Direct-action
descriptive ads Competitive ads
retail ads
Pioneering ads
Image/celebrity Persuasive ads
Point-of-purchase
Jingles and slogans ads
Comparative ads ads
Announcements Demonstration
Testimonials Price deal offers
of benefits

Confirmation
Reminder ads
Informative ‘why’
ads

Figure: Examples of different types of advertising over adoption process stages

Major advertising media:
 Magazine
 Television
 Newspaper
 Yellow Pages
 Radio
 Outdoors
 Cinema
 Internet

Direct-response promotion
 Special considerations with ‘direct marketing’
 Direct communication between a seller and the individual customer using a promotion
method other than face-to-face personal selling
 Started with mail advertising, but has evolved to include other media
 Distinctive feature—It attempts to evoke a direct response from the customer
 Closely tied to the use of a database to target customers
Advertisement in Pharmaceutical of Bangladesh:
 Not allowed for general products in Public newspaper
 Few OTC drug can publish in newspaper
 Advertisement can be published in Medical journal

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  Sales Aid/Literature/Detail aid are a form of advertisement which are used during
personal selling
Do’s & Don'ts of Promotional Material development in Bangladesh
 No promotional material should contain any unspecified assertion or promise.
 Promotional information must be clear, accurate, up to date, balanced and sufficiently
complete to enable the recipient to form their own opinion of the value of the product
concerned.
 Information on product safety as well as contraindication, warning and side effects must be
those approved by the Regulatory Authority.
 Descriptions such as "no contraindication" and "no side effects" are prohibited
 Core safety information to be mentioned in promotional material should contain the
following components: - indication - contraindication - dosage and administration -
precaution and warning - side effect - drug interaction - storage condition.
 Information, promotional claims, supporting data and audio, graphic or other visual
presentation must not be directly or indirectly misleading by omission of certain parts or by
the distortion of evidence or. Expert opinion.
 Making unqualified superlative claims such as "excellent" (e.g., "Product/ Active Ingredients
X is the best treatment for condition Y") are not allowed.
 Information to support promotional claims must always be readily available and must be
promptly provided in response to any reasonable requests.
 Any comparison made between different products must be fair, based on relevant and
comparable aspects of the products, and must not be misleading or disparaging.
 'Hanging' comparatives, which without having any appreciable reason, merely claim that the
product is 'better', 'stronger' etc. must not be used.
 Person's name, photographs or a prominent portrait must not be used in a promotional
material by which one individual can be identified.
 Relevant human figures may be used in promotional materials subject to local law and
regulation. Such illustration should respect the tradition, culture and social value of people of
Bangladesh.
 Minimal information on clinical studies should be provided: Methodology of the study,
Dosage, Number of Patients included, Duration of the treatment and follow-up, Statistical
significance. Primary endpoint should always be presented first (no exclusive focus on
secondary endpoint)
Direct-response online:
 Many promotional mixes now include an advertiser’s Web site and a viewer can respond by
clicking to obtain more detailed information.
 Information might include pictures, videos, sound, text, order entry and so on.
 A small subset of the total number of Web sites account for a large percentage of the
potential audience.
 Portals are Web sites that act as a gateway to the Internet.

292
 Sales promotion

 Promotion activities (other than advertising, publicity and personal selling) that stimulate
interest, trial or purchase.
 May be focused at channel members, final customers or users, or employees.
 Skill may be difficult to develop inside the company, since a promotion activity is often
designed and used only once.
 Sales promotion spending is increasing and exceeds advertising spending

Aimed at final consumers Aimed at intermediaries

or users Aimed at company’s own
Price deals sales force
Contests
Promotion allowances Contests
Aisle displays
Sales contests Bonuses
Samples
Calendars Portfolios
Trade shows
Gifts Displays
Point-of-purchase
materials Trade shows Sales aids
Banners and streamers Meeting Training materials
Trading stamps Catalogues

Sponsored events Merchandising aids

Figure: Examples of sales promotion activities.

Sponsorship
 An investment in cash or kind, in an event, sport, art, person or idea, in exchange for
access to the commercial potential of that event, sport, art, person or idea.
 Not a new concept (traced back to Ancient Rome and Gladiatorial Games).
 Sport sponsorship is by far the most intensive form of sponsorship.
 A wide range of possible objectives.
 A general lack of rigorous evaluation by sponsors.
Pharmaceutical Sponsorship & Events:
 International Conference
 Local Conference
 Meeting/RTD
 Grant & Donation

293
 Public relations and publicity

 Public relations (PR) involves communicating with several interest groups—Employees,

shareholders, governments and political parties as well as customers and the general
public.
 It is aimed at fostering positive publicity and may be used to counter negative publicity.
 Publicity comprises all word-of-mouth (negative or positive) and media coverage.
 There is such a thing as negative publicity (including rumours and myths).

SWOT Analysis

 SWOT analysis is a tool for auditing an organization and its environment.

 It is the first stage of planning and helps marketers to focus on key issues.
 SWOT stands for
• STRENGTHS,
• WEAKNESSES,
• OPPORTUNITIES AND
• THREATS.
 Strengths and weaknesses are internal factors. Opportunities and threats are external factors.
SWOT Analysis

Strengths: Opportunities:
 Vertical integration, core  Digital convergence
competence  Growing mobile device market
 Strong innovative ability  Growing market share in all major
 Faster new product releasing categories
time interval  Better connection with customer

Weakness:
Threats:
 Low brand image due to rising
from a low-cost OEM  Many rivals in leading position
 Not participating in related  Shorter product lifecycle
software industry  Large investment in infrastructure
 Ineffective marketing  Internal disagreement of brand role
communication

294
 PEST Analysis

Political  Market regulations

P Factors 

Taxation
Consumer protection
 Governmental decision
Economic  Exchange rate (1$=2,65 Reals)
E Factors 

Unemployment rate (34%)
Consumer trust
Social  Number of older people increases
S Factors  Illiteracy rate = 5%

Technological  Lower energy costs

T Factors 

Easier access to internet
Mobile technology increasing
Environmental  We can only produce x levels of CO2
E Factors 

Ozone layer worsened this year
Be careful using radon gas

Legal  Employees should sign a confidentiality

L Factors agreement in order to keep the company’s
information secretly

Marketing information system

A marketing information system (MIS) is a management information system (MIS) designed

to support marketing decision making. Jobber (2007) defines it as a "system in which marketing
data is formally gathered, stored, analysed and distributed to managers in accordance with their
informational needs on a regular basis.

295
Structure of MIS:

Four basic or main components of Marketing

Information System (MIS)

Marketing Marketing Marketing

Internal Records
Intelligence Research (MR) Support System

Provides reliable Collects Is used to solve Are tools which helps

internal or inside information from specific marketing marketing managers
information of the the external problems of the to analyze data &
company. sources. company. take better marketing
decisions.

Segmentation, Targeting & Positioning

Market segmentation is a marketing strategy which involves dividing a broad target market into
subsets of consumers, businesses, countries that have or are perceived to have common needs,
interests, and priorities, then designing and implementing strategies to target them.

296
Steps in market segmentation, Targeting, and positioning:

Market segmentation
1. Identify bases for segmenting
the market
2. Develop segment profiles

Market Targeting
3. Develop measure of segment attractiveness
4. Select target segments

Market Positioning
5. Develop positioning for target segment
6. Develop a marketing mix for each
segment

The 10 Elements of a Good Marketing Plan

A good Marketing Plan includes these 10 elements:

1. Describe Your Business.
2. Conduct a Situation Analysis.
3. Define Your Customer.
4. Strategize Your Market Entry.
5. Forecast your Sales or Demand Measurement.
6. Define Your Marketing Budget.
7. Integrate Your Marketing Communication.
8. Identify Sales Channels.
9. Track Marketing Activities.
10. Evaluate Your Progress.

297
Differences between marketing and sales
Marketing Sales

Marketing is one to many Sales is about one to one

Marketing tells the stories (company, product, Sales is where our business becomes real for
etc.) to many people the client. It is where the stories and brand
come to life.
Marketing looks after the brand’s reputation. Sales develops relationships. It’s relationship-
driven.
Marketing analyses the big data. Marketing Sales deals with the ambiguities and the
brings you the average result not the specifics. details of each person. It cannot be averages.
Strategy: pull Strategy: push

Responsibilities of Product Executive (PMD)

 Therapeutic research and new product launching.

 Prepare promotion plants and develop promotional materials.
 Analysis of marketing strategy and market expansion.
 Develop yearly marketing plan of assigned products and convert marketing plan to monthly
action plan.
 Sales monitoring and minimize the problem.
 Setting target for field forces.
 Conduct meeting, scientific seminar and training session.
 Liaise and coordinate with other departments e.g. production, regulatory, medical, product
developments etc.
 Participate actively in lectures, seminars, symposia etc., to enhance product and
organizational image and build rapport with key customer groups.
 Facilitate in the development of annual budget planning.
 Designing of product promotion inputs.
 Explain usage of promotional tools to sales team members.

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 Chapter- Twelve

Pharmaceutical calculation

Ratio, proportion and variation

1. If a 3 tablets contain 975 mg of aspirin, how many mg should be contained in 12 tablets?

Answer.
3 (tablets)
12(tablets)
= 975 mg/ x mg or, x= 3900 mg
2. If a 3 tablets contain 975 mg of aspirin, how many tablets should contain in 3900 mg?
[Ans: x= 12 tablets].

3. If 10 pints of a 5% solution are diluted to 40 pints, what is the percentage strength of the
dilution?
Answer. 10 pints x (%)
= or, x= 1.25%
40 pints 5%

Patient compliance
1. What is the percent compliance rate if a patient received a 30-days supply of medicine and
returned in 45 days for a refill?

Number of days supply of medication

% compliance rate= ×100%

Number of days since last Rx refill

30 days
% compliance rate = = ×100% = 66.6%
45 days

299
 Specific Gravity calculation

Weight of substance
Specific Gravity =
Weight of equal volume of water

1. A 50 ml pycnometer is found to weight 120g when empty, 171g when any filled with water, and 160g
when filled with an unknown liquid, calculate the specific gravity of the unknown liquid?

Answer.
Weight of water: 171 g – 120g = 51g
Weight of unknown liquid: 160g – 120 g = 40g
40g

Specific gravity of liquid = = 0.78

51g

2. If a pint of a certain liquid weighs 601gm, what is the specific gravity of the liquid?
Answer.
1 pint = 16fl. oz.
16 fl.oz. of water weighs 473gm

601
Specific gravity of liquid = = 1.27
473

Specific volume calculation

1. Calculate the Specific volume of syrup, 91.0 ml of which weighs 107.16?

Answer.
107.16 g of water measures 107.16ml

300
 91.0 ml
Specific volume of syrup = = 0.849 ml
107.16 ml

Density calculation
Mass

Density =
Volume
1. Calculate the density of 10ml of sulfuric acid weigh 18 g?
Answer.
18g
Density = = 1.8g / ml
10ml

Weight in volume calculation

1. How many grams of dextrose are required to prepare 4000 ml of a 5% solution?
Answer.
4000 ml represents 4000 g of solution. Or, 5g / 100 ml× 4000ml = 200 g
5% = 5/ 100 = 0.05
4000g × 0.05 = 200 g

Weight in weight calculation

1. What Weight of a 5% (w/v) solution can be prepared from 2g of active ingredient?

Answer. 5% 2g
= x = 40 g
100% xg

301
 Formula calculation

General formula:
Weight required × percentage required

Total percentage used

1. From the formula calculate the quantity of each ingredient required to make 1000 g of the
ointment?

Coal Tar 5 parts

Zinc oxide 10 parts
Hydrophilic 50 parts
Answer.
Total number of parts = 65
1000 g will contain 65 parts
65 (parts) 1000 (g)
=
5 (parts) x (g)
X= 76.92 g of coal tar
65 (parts) 1000 (g)
=
10 (parts) y (g)
y= 153.85 g of zinc oxide
65 (parts) 1000 (g)
=
50 (parts) z (g)

z = 769.23 g of Hydrophilic ointment

Total= 76.92 g + 153.85 g + 769.23 g = 1000 g

302
2. From the following formula, calculate the quantity of each ingredient required to make 240 ml of
calamine lotion.
Calamine 80 g
Zinc oxide 80 g
Glycerin 20 g
Bentonite magma 250 ml
Answer. 80 g
Calamine = × 240 ml = 19.2 g
1000 ml
80 g
Zinc oxide = × 240 ml = 19.2 ml
1000 ml
20 g
Glycerin = × 240 ml = 4.8 ml
1000 ml
250 g
Bentonite magma = × 240 ml = 60 ml
1000 ml
Calcium hydroxide topical solution to make 1000 ml.

pH calculation

1. Calculation the pH of a solution if the hydrogen ion concentration is 1.8 × 10-5 mol/ liter.
Answer.
pH = - log [H+]
= - log (1.8× 10-5)
= 5- log (1.82)
= 5-0.260
= 4.74

303
2. Calculation the pH of a solution if the hydroxyl ion concentration is 5×10-4 mol/liter.

Answer. Kw
[H+] =
[OH-]
1×10-14
= = 2× 10-11
5× 10-4

pH = - log [H+]
= - log (2×10-11)
= 11-log2
= 11-0.301
= 10.69
3. Calculation the pH of 0.1 N NaOH.
Answer.
POH =log [OH]
= - log (0.1) = 1
pH= 14- pOH
= 14- 1 = 13

Normality and Molarity calculation

General formula moles of solute

Molarity =
Liters of solution
1. 5.30 gm of Na2CO3 was dissolved in water the volume after solution made to 100 ml. calculate
Normality and Molarity of the solution.
Answer.
Molecular weight of Na2CO3 = 106
100 ml solution contain = 5.30 gm Na2CO3
1 ml solution contain = 5.30/ 100 gm Na2CO3

304
1000 ml solution contain = 5.30/ 100 × 1000 gm Na2CO3
= 53 gm
Molarity = weight of Na2CO3 / mw
= 53/ 106
= 0.50
Normality = Molarity × 2
= 0.50 × 2 = 1

Half-life calculation
1. Calculation t1/2 and t10%.
Answer. 2.303 Co Co= Initial concentration
t1/2= log
K C C= Final concentration
2.303 100
t1/2= log
K 50

2.303
t1/2= log 2
K
2.303
t1/2= × 0.301
K
0.693
t1/2=
K
2.303 Co
T10% = log
K C

305
 2.303
T10% = log (1.111)
K
2.303
T10% = × 0.0457
K
0.1043
=
K
0.1043 0.693
= × t1/2 [K= ]
0.693 t1/2
2. Calculate the elimination rate constant for a drug having an elimination half-life of 1.7 hours.
Answer. Elimination rate constant (Kel) for a drug is given by the formula.

0.693 0.693
Kel = = Kel = 0.407 hr-1
t1/2 1.7

Bioavailability calculation

1. If the AUC for an oral dose of a drug administrated by a tablet is 4.5 mcg/ml and the intravenous dose
is 11.2 mcg/ml, calculate the bioavailability of the oral dose of the drug.
Answer. AUC oral tablet
F=
AUC IV
4.5 mcg/ml
= = 0.4 = 40%
11.2 mcg/ ml

306
 Volume of distribution calculation
1. A patient received an intravenous dose of 10 mg of a drug. A blood sample was drown and it
contained 40 𝜇g / 100 ml. calculate the apparent volume of distribution for the drug.
Total amount of drug in body (DB°)
Vd=
Blood (plasma) concentration (Cp°)
Answer. D
Since, Vd =
Cp Here,
10 mg Cp = 40 𝜇g / 100 ml
Vd= Or, 0.04 mg / 100 ml
0.4 mg/liter Or, 0.4 mg/liter
=25 liters

2. If 150 mg of a drug is administered intravenously and the resultant drug plasma concentration is
determine to be 2.5 𝜇g/ml. calculate the apparent volume of distribution. [Ans: 60 liters]

Creatinine clearance calculation

1. A female patient weighing 70 kg and 65 years old, has serum creatinine level 2 mg/dL, what is the
expected creatinine clearance rate. Calculate the CrCl for a female patient.
Answer.
For female patient, the creatinine clearance rate is 0.9 × CrCl for males.

98 - 0.8 (age – 20)

CrCl for males =
Serum creatinine (mg/dL)
98 - 0.8 × (65 – 20)
CrCl for males =
2 mg/dL

307
 98 - 0.8 × 45
CrCl for males =
2 mg/dL
98 – 36
CrCl for males =
2 mg/dL
= 31 ml / min
CrCl for females = 0.9 × 31 ml / min
= 27.9 ml / min
2. What is the creatinine clearance for a 25-years-old male patient with a Ccr of 1 mg / dL? The patient is
5 ft, 4 inches in height and weighs 103 kg.
The patient is obese and the Clcr calculation should be based on ideal body weight.
50 kg + [2.3 × 4]
LBW (males) =
Kg = 59.2 kg
Using the Cockcroft and Gault method the Clcr can be calculated.
[140- age (yr)] × body weight (kg)
Clcr=
72 (Ccr)
(140-25) × (59.2 kg)
Clcr =
72 (1)
= 94.6 ml / min

308
  Lean body weight (LBW) (male) = 50 kg + 2.3 kg for each inch over 5 ft
 Lean body weight (LBW) (female) = 45.5 kg + 2.3 kg for each inch over 5 ft
 Jellife method: 98-0.8 (age-20)
Clcr=
Ccr
 Crockcroft and Gault method: [140-age (yr)] × body weight (kg)
Clcr = 72 (Ccr)

Dose calculation
General formula Total amount
Number of doses =
Size of dose
1. If the dose of a drug is 500 mg, how many doses are contained in 20 g?

Answer.
20 g = 20,000 mg
20,000 mg
Number of doses= = 40 doses
500 mg
2. If 1 tablespoon is prescribed as the dose, approximately how many doses will be contained
in 1 pint of the medicine?

Answer,
1 tablespoon = 15 ml
1 pint = 473ml
309
 473ml
Number of doses = = 31 doses
15ml
2. The usual dose of azithromycin is 175 mcg/kg of body weight. What amount of drugs should
be administrated to a person weighing 185 Ib?
Answer,
175 mcg = 0.175mg

0.175 mg
Patient dose = 185Ib× [1kg= 2.2Ib]
2.2Ib
= 14.71mg
= 15mg
3. If the dose of a drug is 200 mg, how many doses are contained in 10gm? [Ans- 50 doses]

Stock solution calculation

1. How many milliliters of a 1: 400 w/v stock solution should be used to make 4 liters of a 1: 2000 w/v
solution?
Answer:
4 liters = 4000 ml
1:400 = 0.25%
1:2000 = 0.05%
0.25% 4000 ml
= x = 800 ml
0.05% x

2. How many milliliters of a 1:400 w/v stock solution should be used in preparing 1 gallon of a 1:2000
w/v solution?

310
Answer:
1 gallon = 3785 ml
1:400 = 0.25%
1:2000 = 0.05%
0.25% 3785
= x=757
0.05% x

3. Preparation of 50 ml of 5% methanol solution from 98% stock solution.

Answer:
Methanol’s strength S1= 5%
Volume V1 = 50 ml
Stock methanol’s strength S2= 98%
Methanol’s volume V2 =?
We know, V1S1 = V2S2
V1S1
V2 =
S2
50 × 5
= = 2.50 ml
98

Potency calculation
1. How much Ranitidine Hydrochloride is required to manufacture 15, 00000 tablets. The potency of
Ranitidine Hydrochloride is 98.35%. Standard quantity of Ranitidine Hydrochloride is 250.50 kg.
Answer:

Standard quantity
Required quantity = × 100
Potency

311
 250.50
= × 100
98.35
= 254.7025 Or, 254.705 kg.

1. The concentration of drug additive in an animal feed is 12.5 ppm. How many milligrams of the drug
should be used in preparing 5.2 kg of feed?
Answer. 12.5 ppm = 12.5gm (drug) in 1,000,000gm (feed)
Thus,
1000000gm
12.5
= 5200gm/ x mg = 0.065 gm.

Splitting tablets

1. A patient attempted to split in half 20 mg unscored tablet of a drug, resulting in “half-tablets”

different by 1.5 mg in drug content. Assuming a whole tablet was uniform in drug content, calculate
the amount of drug in each “half-tablet”.
If L= larger half and S= smaller half
Then L+S = 20 mg
L- S = 1.5 mg

2L = 21.5 mg
L= 10.75 mg and S= 20 mg – 10.75 mg = 9.25 mg.

312
 Chapter- Thirteen

Pharmaceutical Dictionary

Abbreviated New Drug Application (ANDA): An Abbreviated New Drug Application

(ADNA) contains data that, When submitted to FDAs center for Drug Evaluation and Research,
provides for the review and ultimate approval of a genetic drug product in the United States.
Abrasion Test: The measurement of abrasion resistance, usually by the weighing of a material
sample before and after subjecting it to a known abrasive stress throughout a known time period,
or by reflectance or surface finish comparisons, by dimensional comparisons.
Accelerated Testing: Studies designed to increase the rate of chemical degradation or physical
change of an active substance or pharmaceutical product by using exaggerated storage conditions
as part of the formal stability.
Accuracy: The accuracy express the closeness of agreement between the value which is
accepted either as a conventional true value or an accepted reference value and the value found
obtained by applying the test procedure a number of times.
Acid Value: Number of milligrams of potassium hydroxide required to neutralize the free acid in
one gram of the substance.
Action limit: The action limit is reached when the acceptance criteria of a critical parameter
have been exceeded. Results outside these limits will required specified action and investigation.
Active pharmaceutical ingredients (API): An active pharmaceutical ingredients is any
component that provides pharmacological activity or other direct effect in the diagnosis, cure,
mitigation, or prevention of disease, or to affect the structure or any function of the body man or
animals.
Actual Yield: The quantity that is actual produced at any appropriate phase of manufacture,
processing, or packaging of a particular drug product.
Additive: Substances added to the formulation to prepare a dosage form. These are added to a
dosage forms to enhance stability, usefulness, elegances to facilitate its preparation and also for
better bioavailability.
Admixture (intravenous): Intravenous fluid with one or more drugs added for administration to
patient.
Adsorbent: A drug that binds other chemicals onto its surface, used to reduce the free
availability of toxic chemicals, e.g. Activated charcoal, Kaolin.
Adsorption: The action of a substance in attracting and holding other material or particles on its
surface. It is adhesion by a gas, liquid or solute to surface of a solid.

313
Adverse reaction: An unwanted effect reasonably associated with use of drug that may occur as
part of the pharmacological action of the drug or may be unpredictable in its occurrence.
Air Lock: A room or space designed to act as a means of segregating areas of different air
classification or quality. It may contain a method to remove particulate contamination from clean
room garments as personnel pass through, and usually includes HEPA filtered air supply and
interlocking doors.
Amorphous: Solid substances those are not crystal. Amorphous solids consists of randomly
oriented molecules.
Ampoule or Ampule: A small glass vial sealed after filling and one of the earliest device
developed for safe storage of sterile injectable able unit.
Annual Product Quality Review (APQR): Annual product quality review is defined by a
documented review procedure of a product quality when carried out of product annually.
Antibody: Antibody is serum protein which is formed in the blood, lymph and various
secretions of the body in response to antigenic stimuli and reacts specially with that antigen in
some observable manner in vivo and vitro.
Antidote: A drug that reduces the effects of ingested poisons. E.g. Activated Charcoal
Antigen: A molecule that is capable of interacting with specific components of the immune
system.
Antiseptics: It is a substance that inhibits the growth and development micro- organisms without
necessarily destroying them.
Area under the Curve (AUC): The area under the curve of a plot of drug concentration in
plasma against time. The AUC taken to infinity can be used to determine the bioavailability of a
drug product.
Assay: A technique (test) for measuring how much of some particular material is the sample.
Assay is always quantitative.
Baffle: Metallic Plates usually attached to walls of vessels to help direct the flow of a fluid being
mixed. Baffles are added to coating pans.
Batch (Lot): A specific quantity of material produced in a process or series of processes so that
it is expected to be homogeneous within specified limits. In the case of continuous production, a
batch may correspond to a defined fraction of the production. The batch size can be defined
either by a fixed quantity or by the amount produced in a fixed time interval.
Bioassay: The determination of the biological activity of a substances (e.g. a drug) by observing
its effect on an organisms (or organ) compared to a standard preparation.
Biochemical oxygen Demand (BOD): The amount of oxygen required to oxidize the dissolved
organic matter in a water sample by aerobic (bacterial) decay.

314
Bioavailability: Bioavailability means the rate and extent to which the active substance or active
moiety is absorbed from a pharmaceutical form and becomes available at the site of action.
Bioequivalence: If two or more similar dosage form of a drug reaches the general circulation at
the same relative rate and the same relative extant, they are bioequivalent. Two drug products are
considered bioequivalent if they exhibit the ‘same’ Cmax, Tmax and AUAC in properly powered
pharmacokinetics study. If two drug products are bioequivalent then it is assumed that they are
therapeutically equivalent.
Bioinformatics: The use of computer in the life sciences, electronic databases of genomes and
protein sequences, and computer modeling of biomolecules and biologics systems.
Bipolar disorder: If a patient one or more manic episodes the condition may be termed a bipolar
disorder.
Blister: Term used in inspection of glass or plastic containers: a relative large flat bubble,
usually near the surface.
Body surface Area (BSA): A measure used to calculate, normally pediatric doses.
Surface of the patient (m2)
Approximate pediatric doses = × Adult dose.
1.8
Boluses: Boluses are large elongated tablets intended for administration to animals.
Blow Fill Seal (BFS): It is a technology refers to the manufacturing technique used to produce
small (0.1ml) and large volume (500ml) liquid pharmaceutical liquid dosage form. The
technology can be used to aseptically manufacture pharmaceutical liquid dosage form.
Bubble Point: Nondestructive integrity test of a filter membrane based on the amount of
pressure required for the force air through a wet porous membrane.
Buffer: A substance capable of neutralizing both acids and bases in solution, thereby
maintaining the original acidity or causticity of the solution.
Buffer Solution: A buffer solution to resist changes in pH upon the addition of acid or alkali.
Bulk density: Characteristic of a powder rather than of individual particles given by the mass of
powder occupying a known volume.
Bulk Product: Any product that has completed all processing stages up to, but not including,
final packaging.
Cachets: It is a solid preparation consisting of a hard shell containing a single dose of one lore
more active substances.

315
CFU (colony forming unit): A measure of the number of a bacteria present in the environment
or on the surfaces of an antiseptic processing from, measured as part of qualification and ongoing
monitoring.
Change Over: The program by which a processing area is cleared of supplies and components
used in the manufacture of previous product and then readied for production of a new product
.This often includes parts change over and/or special cleaning to eliminate cross contamination.
Changing room: Room designed for the changing of clothes and from which clean or ascetic
area is entered.
Chelating agent: A complexing agent that binds metal ions into stable ring structures useful in
treating poisoning. E.g. Edetate calcium disodium.
Chromophore: Chromophore is group which when attached to a saturated hydrocarbon
produces a molecule that absorbs maximum amount of visible or UV energy at some wave
length.
Compressibility: Ability of a power to describe is volume under pressure.
Controlled release: This dosage forms release drug at a constant rate and provide plasma
concentrations that remain invariant with time.
Contact angle: The angle formed by the solid surface and the tangent line to the upper surface at
the end point is called the contact angle.
Co-Solvent: Substance added to a solution to increase the solubility of hydrophobic solute e.g.
sorbitol, Glycerin.
Critical control point (CCP): A step of a starting material, intermediate product or finished
product with another starting or product during production.
Crystal habit: It is the description of the outer appearance of a crystal, such as platy, needle,
cubical, prismatic, blade, tabular etc.
Deflocculation: Reversal of coagulation or flocculation i.e. the dispersion of aggregates to form a
stable colloidal suspensions or emulsion.
Deformation: Change is geometry of solid when it is subjected to opposing force.
Elastic deformation: Deformation that is spontaneously reversible when the external forces are
removed.
Plastic deformation: Deformation that is nit reversible when the external forces are removed.
Denaturation: The loss of the native structure of a macromolecule resulting, form heat
treatment, extreme pH changes, chemical treatment, etc. It is accompanied by loss of biological
activity. For example, proteins may be denatured by heat, p H extremes, or addition of agents such
as urea or guanidinium hydrochloride.

316
Dew Point: Temperature to which a given mixture of air and water vapor must be cooled to
become saturated.
Dispensing: The pouring or transferring of any material from a container, tank or similar vessel,
whereby vapors, dusts, fumes, mists or gases may be liberated to the atmosphere.
Disintegrant: An excipient that facilitates the disintegration of a tablet or other dosage form in
contact with water or gastrointestinal fluid. Traditionally starch was used, but in general todays
formulations utilize a so called super disintegrant such as croscarmellose sodium or sodium
starch glycolate.
Disinfectants: It is a chemical substance that is used in stronger concentrations to kill microbes.
DOP (dioctyl phthalate/dispersed oil particulate): A mono-dispersed test aerosol of sub-
micron particles, generated to challenge (evaluate integrity) of HEPA filters for HVAC.
Dosage form: Unit containing the dose of drug. This is the prepared from of a drug g taken in
fixed quantity and is used for treatment. Tablets, capsules are dosage forms. We cannot take a
drug without form.
Dose: Dose is the predetermined amount of drug that is administrated for therapeutic use.
Douches: Douches are column of fluid of a certain nature and temperature, allowed to fall on a
part of the body.
Drug Holiday: Discontinuance of a therapeutic drug for a limited period of time. Sometimes
used as a way of evaluating baseline behavior or as a means of controlling or reducing the
dosage of psychoactive drugs and side effect. It is not popular now. Earlier it was used in the
treatment of Parkinson’s diseases.
Drug interaction: The effect of two or more drugs taken simultaneously, producing an alteration
usual effect of either drug taken alone. The interacting drug may have potentiating or additive
effect and serious side effect may result. An example of drug interaction is alcohol and sedative
drugs taken together, which may cause central nervous system depression.
Drug master file: A drug master file is a means of providing data on a processing facility, drug
substance, packaging material, or excipient confidentially to FDA. The data in a DMF can be
accessed by FDA in the support of an NDA upon provision of a letter of accesses.
D- Value: The time under a stated set of exposure conditions (temperature in an autoclave)
required to reduce a microbial population by a factor 90% (e.g. from 10,000 to 1,000).
Dwell Time: Period of time when a sterilizer is at or above the set temperature.
Dry Powder Inhaler (DPI): A dosage form for delivery of drug to the airways consisting of
micro ionized respirable drug, usually dispersed on lactose as a carrier and packaged into a single
dose or multiple dose device.
Effervescent Tablet: A dosage form containing ingredients that rapidly release carbon dioxide
when in contact with water.

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Effluent Treatment Plant (ETP): Effluent treatment plant treats the waste materials into
neutralized molecule into neutralized or reduces the harmful ingredients. Industrial wastewater
treatment covers the mechanisms and processes used to treat wasters that have been
contaminated in some way by anthropogenic industrial or by commercial activities prior to its
release into the environment or its reuse.
Ejection force: The force necessary to ejection finished tablet from the ejection tablet die.
Elixir: A clear, sweetened usually hydro alcoholic liquid containing flavoring substances and
active medicinal agents used orally as vehicle or for the effective of the medicinal agent
contained.
Emollient: An agent that softens or soothes the skin, or soothes an irritated internal surface. E.g.
Fixed oil, Wax in cold cream.
Emulsifier: Stabilize of the droplet from of the internal phases of an emulsion.
Emulsion: Emulsion may be defined as biophasic system comprising of two immiscible liquids
usually water and oil, one of which is finely subdivided and uniformly dispersed as droplets
throughout the other.
Excipient: A component of a drug product other than the API, that is intentionally added to the
dosages form to enable processing into patient friendly medicines, to control the rate at which the
API dissolves from the dosage form to aid drug stability and other reasons.
Expiration date: The date placed on the immediate or primary container label of a drug product
that designates the date through which the product is expected to remain within specifications.
Factory Acceptance Test (FAT): Contractual test usually done by the supplier before delivery.
FIFO: FIFO is an acronym for first in, First out, A method for organizing and manipulating a
data buffer, or data stack, where the oldest entry , or ‘bottom’ of the stack is processed first. It is
analogues to processing a queue with first come, first served behavior: Where the people leave
the queue in the order in which they arrive.
Flame Projection Test: This test indicates the effect of an aerosol formulation on the extension
of an open flame. The product is sprayed for about four seconds into a flame and extension of the
flame length is measured by a ruler.
Flocculation: A technique for liquid/solid separation. Cationic or anionic polyelectrolytes are
added to highly colloidal water causing coagulation and subsequent settling. The phenomena
could be charge neutralization or a bridging effect between separate particles.
Fusion Welding: Fusion welding is a generic term for welding processes that rarely upon
melting to join materials of similar composition and melting points. Due to the high temperature
phase transitions inherent to these processes, a heat- affected zone is created in the material often
minimize this effect by introducing comparatively little heat in to the work piece.

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Gastritis: It is the inflammation of gastric mucous membrane. Acute gastritis may be caused by
aspirin, alcohol, butazolidine etc. Clinical features include nausea, vomiting, haematemesis and
melena.
Gel: It is semisolid system consisting of either suspension made up of small inorganic particles
or large organic molecules interpenetrated by a liquid intend to administer drugs topically or into
body cavities.
General Agreement on Trade and Tariffs (GATT): The General agreement on trade and
tariffs was fort signed in 1947. The agreement was designed to provide an international forum
that encouraged free trade between member states by regulating and reducing tariffs on trade
goods and by providing a common mechanism for resolving trade disputes. GATT membership
now includes more than 110 countries.
General drug: A drug for which the patents protecting the originator product have expired.
Generic products are pharmaceutically equivalent to a reference listed drug (some drug
substance, same route of administration, same dosage form and same strength) and are also
therapeutically equivalent (typically bioequivalent for oral solid dosages forms). A generic drug
can be solid only after a proprietary drug goes off patent (i.e. when the patent runs out after 17
years).
Grandfather drug: Drug brought to market before 1938. These products are allowed to be solid
without providing safety or effectiveness data, because they are generally recognized as safe and
effective-provided no evidence to the contrary develops.
HACCP (Hazard Analysis on Critical control points) plan: A document prepared in
accordance with the principle of HACCP to ensure the control of hazards which are significant
for pharmaceutical quality in the production and supply chain.
Hormones: Substance secreted by endocrine tissue into the blood that acts on a target tissue to
produce a specific response. These are glandular secretion that stimulates one or more specific
organs in the body to fulfill their function.
Human Machine Interface (HMI): Human machine interface, a panel used for communication
with the BMS (Building Management System). May be located outside the field panel, or may be
portable. Note that portable HMI usually do not have an audit trail for changes, and should be
used as view only.
Hybridization: The process of joining two complementary strands of DNA or one each of DNA
and RNA to form a double-stranded molecule.
Hydrocortisone: Major Corticosteroids are produce and secreted by adrenal glands.
Hydrocortisone assists in metabolism of carbohydrates, fats and proteins and body’s reaction to
stress. It helps in severe allergy, asthma, eczema and inflammation.
Hypertonic solution: The solutions which have a greater osmotic pressure than blood or 0.9%
sodium chloride solution.

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Hypodermic tablet: Hypodermic tablets are composed of one or more drug with other readily
water- soluble ingredients and one intended to be added to sterile water for injection.
Hypotonic Solution: The solutions which have lower osmotic pressure than blood or 0.9%
sodium chloride.
IBC (Intermediate Bulk Container): A Container for storing, transporting and handling dry
materials. Normally bigger than ½ cubic meter but smaller than 3 cubic meters, dust free, able to
receive and discharge a variety of materials and capable of automaton.
Impeller: Device containing blades for fluid mixing. Several designs such as radical flow, mixed
radial-axial are commonly used.
Incubator: An apparatus for maintaining a premature infant, eggs, microorganisms or other
living cells.
Indicator: Substance added to sample being analyzed to determine the completeness of a
chemical reaction. Chemical indicators show a visible color at the reaction is complete.
Inert Gas: Nitrogen and carbon dioxide are known as inert gases. The phrases is also used to
refer to uncreative gasses such as helium, neon, argon, krypton, xenon and radon.
Infusion: The introduction of a substance, such as drug, saline, nutrient, or other solution into
bloodstream or a body cavity for therapeutic purposes. Single dose large volume parenteral
(LVP) containing more than 100 millimeters.
Injection: A preparation intended for parenteral administration and / or constituting or diluting a
parenteral article prior to administration. The introduction of parenteral may be into the
subcutaneous cellular tissue (subcutaneous or hypodermic), or the muscular tissue.
Inhalations: Inhalations are drugs or solutions or suspensions of one or more drug substances
administered by the nasal or oral respiratory route for local or systemic effect.
INN (international nonproprietary names): Nomenclature activity sponsored by the world
health organization, which has developed a procedure and guiding principles for the selection of
international nonproprietary names.
Intrauterine device (IUD): Intrauterine devices have been developed using modern technology
that allows uniform release of drug over a much longer period of time.
Isotonic solution: It is solution that has same osmotic pressure as blood or 0.9% sodium chloride
solution.
IUPAC (international union of pure and applied chemistry): Organization that recommends
a comprehensive system of nomenclature for chemical compounds.
Kaolin: A negative hydrated aluminum silicate, which is commonly used as an adsorbent in
diarrhea patients.

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Lactose intolerance: The normal reduction in lactase activity in mature mammals that results in
lactose not being cleaved into glucose and galactose in the gastrointestinal tract. Cleavage is
necessary for absorption because lactose itself is not absorbed and passes into the large intestine
where it causes symptoms of bloating.
Lactose: A di-saccharide commonly used in pharmaceuticals tablets and capsules as a diluents
or filler binder and extensively used in dry powder inhalers as a carrier.
Lag time: The period which elapse between the time of administration of a drug and the start of
absorption or the time a measurable concentration is found in the blood.
Large Volume Parenteral (LVP): Single-dose dosages form that is intended for parenteral use
and is packaged in containers holding 100ml or more. USP limits injection to 1000ml.
Laxative: A drug that promotes defection, usually considered milder in action than a cathartic
e.g. Methyl cellulose, Mineral oil.
Leach: To dissolve by the action of a moving liquid. For example, high purity water leaches
trace impurities from glass vessels.
Lethal dose: Amount of dose that causes death of some experimental animal.
Limit of detection (LOD): The lowest amount of analyte in a sample, which can be detected but
not quantitated as an exact value. The LOD is mostly a parameter of limit tests.
Limit of Quantitation (LOQ): The quantitation limit of an individual analytical procedure is
the lowest amount of analyte in a sample, which can be quantitatively determined with suitable
precision and accuracy. The quantitation limit is a parameter of quantitative assays for low levels
of compounds in sample matrices, and is used particularly for the determination of impurities
and /or degradation products.
Liniment: liniment are external preparations of a consistency thicker than water, but thinner
ointments, usually applied to the skin with a gentle rubbing of the hands.
Line clearance: Check that the area and equipment to be used for packaging operation is clear of
components and product from a previous operation.
Linearity: The linearity of an analytical procedure is its ability (within a given ranges) to obtain
test results which are directly proportional to the concentration of analyte in sample.
Lotion: Lotions are fluid preparation, usually containing suspended insoluble material and
applied externally.
Lozenges: Solid preparations containing one or more medicinal agents in a flavored, sweetened
base intended to dissolve or disintegrate slowly in the mouth, releasing medication generally for
localize effects.
Lubricants: Lubricants are intended to prevent adhesion of the tablet materials to the surface of
dies and punches, reduces inter particle friction and may improve the rate of flow of the tablet
granulation. E.g. stearic acid, Magnesium stearate, Talc, PEG (polyethylene glycols).

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Lyophilization: Also known as freeze drying, it is means of stabilizing wet substances by
freezing them, then evaporating the resulting ice, to leave a substantially dry, porous residue
which has the same size and shape of the original frozen mass.
Magmas: Magmas are pharmaceutical suspensions in which the suspensions has as high degree
of physical attraction to the aqueous vehicle, forming a gelatinous mixture that maintains that
uniformly and stability of the suspension. Magmas are administrated orally.
Maintenance dose: It is the amount of l a drug given in each dose at certain intervals to replaces
the drug eliminated since the preceding dose to maintain a steady state level of drug in the body.
Medicinal Plant: Medicinal plants are plants used for medicinal purposes.
Mole Fraction: It is the ration of the number of moles of solute to the total number of moles of
the solution.
Mother liquor: The residual liquid that remains after the crystallization or isolation processes.
Mother liquid may contain unrecovered products. It may be used for further processing.
MSDS (Material Safety Data Sheet): Document describing the chemical properties of a
substance as related to its safe handling and storage. The substance manufacturer originates it.
Multi-emulsion: Multi emulsion in which oil in water or water in oil emulsion are dispersed in
another liquid medium.
Nano- Capsules: Nano-capsules are vesicular systems in which the drug is confined to a cavity
surrounded by a unique polymeric membrane.
National Formulary (NF): A compendium of the purity and testing criteria for chemicals,
usually in combination with the USP. It is revised every five years.
Nebulizer: It is device converts drug solution into continuous fine aerosol which can be inhaled
directly in lungs. It delivers high dose of inhaled medication. It uses normal tiding breathing.
Wet aerosol is the choice of therapy.
Normal saline: A very common LVP (large volume parenteral) that has a physiologic (0.9%)
concentration of sodium chloride.
Norplant: It is contraceptive implant. Its six tubes filled with synthetic progestin are implanted
in client’s upper or lower arm. After insertion they are not visible.
Opsonin: Any substance that binds to particulate antigens and induces their phagocytosis.
Orange book: The FDA’s list of approved drug products with therapeutic equivalences is
commonly referred to as “the orange Book”. The FDA’s official publication, it covers, among
other things, approved generic, dose form dossiers, non-antibiotic patent expiries and Waxman-
Hatch extension information for pharmaceuticals in the US. The Orange Book is linked to
Newport’s proprietary intelligence on API manufacturing worldwide.

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Orange Guide: Familiarly known as the Orange Guide, this title is an essential references work
for all those involved in the manufacture or distribution of medicines in or for Europe. It is
compiled by the UK drug regulatory body, the MHRA, and brings together the European and UK
guidance documents and information on legislation relating to the manufacture and distribution
of medicines for human use. It therefore contains EU guidance on good manufacturing and good
distribution practice along with relevant information on EU and UK legislation.
Orphan drug: The FDA grants Orphan Drug status to one company for a drug that is believed
to substantially increase the life expectancy of the treated patient for a particular disease. This
excludes other companies from receiving an FDA license to produce a similar drug for a finite
period (usually 7 years), thereby allowing the company producing the drug to recuperate their
R&D expenses.
Otic Solutions: Otic solutions are intended for instillation in the outer ear and may be aqueous in
nature or may be prepared with glycerin or other solvents and dispersing agents. E.g. Benzocaine
otic solution.
Pellet: Pellets are small spheres of sucrose saturated with an alcoholic tincture, primarily used in
homeopathic medicine.
Pharmaceutical alternatives: Medical products that contain the same therapeutic moiety but
differ in the salt or ester of that moiety or in dosage form or strength.
Pharmaceutical Equivalent: One of drug products that contain the same active ingredients and
that are identical in strength or concentration dosage form and route of administration.
Pilot Scale Batch: A Batch of an active substances or pharmaceutical product manufactured by a
procedure fully representative of and stimulating that to be applied to a full production scale
batch. For solid oral dosage forms, a pilot scale is general is at a minimum, one tenth that of a
full production scale or 1000000 tablets or capsules, whichever is the larger.
PLC (programming logic controller): An automated system with analog capability as well a
binary (discrete). PLCs must be equipped with a digital interface to a ‘front end’ computer for
data collection and for programmer interface.
Poly-alpha-olefin (PAO): Synthetic oil used in lieu DOP for HEPA filter testing.
Positive pressure: Positive pressure is a pressure within a system that is greater than the
environment that surrounds that system. Consequently if there is any leak from the positively
pressured system it will egress into the surrounding environment.
Potency: The amount of drug required to produce a particular magnitude of response. Potency is
a comparative rather than an absolute expression of drug activity. Drug potency depends on both
affinity and efficacy.
Poultices: Poultices are the readymade home preparations that are still in use today. But
currently their uses in retail pharmacy are nearly obsolete. They are ‘slurry’ type preparation and
are also used in a layer on the site of application.

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Powder: Powders are intimate mixtures dry, finely divided drug or chemicals that may be
intended for internal use.
PPM (parts per million): Abbreviation for parts per million, used to describe concentration in
liquids or gases, e.g. 10,000 is approximately equivalent to 10g/litre or a 1% W/V solution.
Prefilter: A filter to trap gross particulates located upstream before a HEPA filter. The
efficiency of initial prefilters usually in the 20% to 30% range by the ASHRAE Atmospheric
dust spot efficiency, while intermediate prefilters usually have a collection efficiency of 80% to
90% by the same test.
Prodrug: The drug which do not produce any pharmacological effect until they are chemically
altered within the body are called prodrug. E.g. Levodopa, Castor oil.
Propellant: Integral ingredient in an aerosol that expels the product and may act as a solvent.
Liquefied gases like halocarbons and other hydrocarbons and compressed gases like nitrogen,
nitrous oxide and carbon dioxide are used as propellants.
Quality: Quality is the totality of features and characteristics of a product or service that bear on
its ability to satisfy stated or implied needs.
Quality risk management: A systemic process for the assessment, control, communication and
review of risks to the quality of the drug (medicinal) product across the product lifecycle.
Quarantine: The status starting or packaging materials, intermediates or bulk or finished
products isolated physically or by other effective means while a decision is awaited on their
release, rejection or reprocessing.
Radiopharmaceutical: A drug containing a radio-isotope, used for diagnostic or therapeutic
purposes. E.g. Iodinated Albumin with 125 I.
Radom sample: Sample in which the different fractions of the material have an equal
probability of being represented.
Raw material: A general term used to denote starting materials, reagents, intermediates, process
aids, and solvents intended for use in the production of intermediates or APIs.
Reagent: A substance used (as in detecting or measuring a component, in preparing a product, or
in developing photographs) because of its chemical or biological activity.
Reconciliation: A comparison making due allowance for normal variation, between the amount
of product or materials theoretically produced or used and the amount actually produced or used.
And the amount actually produced or used.
Reconstitution: Returning a substance its original state, usually by adding water or other fluid to
a dry powder.
Reducing agent: substances that loses electrons easily, causing other substances to be reduced.
E.g. Hydrogen sulfide, Sulfer dioxide.

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Reference standard: Any material of known identity and purity or potency. An official
reference standard is one obtained from an official source such as BP. Or USP, or WHO. A
house reference standard may be obtained by through characterization for identity and purity or
potency relative to an official reference standard, or by determination of absolute purity by other
techniques.
Refractive index: The refractive index or index of refraction n of a substance is a dimensionless
number that describe how light, or any other radiation, propagates through that medium. It is
defined as: n=c/v, where c is the speed of light in vacuum and v is the speed of light in substance.
Relative Humidity: The ratio (measured in percent) of actual water vapor pressure in air to the
pressure of saturated water vapor in air at the same temperature and pressure.
Reprocessing: Subjecting all or part of a batch or lot of an in-process drugs, bulk process
intermediate or bulk product of a single batch or lot to a previous step in the validated
manufacturing process due to failure to meet predetermined specifications.
Retention Sample: Sample collected as part of the original sampling process and reserves for
future testing. The size of a retention sample should be sufficient to allow for at least two
confirmatory analyses. In some cases statutory regulations may require one or more retention
samples, each of which should be separately identified, packaged and sealed.
Reverse osmosis (RO): The reversal of osmosis to purify water. In osmosis, water diffuses
through a semipermeable membrane from a region of higher concentration into one of lower
concentration (such as a solution of water and salt).The flow of water can be reversed with an
opposing pressure that exceeds osmotic pressure.
Reworking: Subjecting an in-process or bulk process intermediate or final product of a single
batch to an alternate manufacturing process due to a failure to meet predetermined specifications.
Rheology: The word ‘rheology’ from the Greek ‘rheos’ meaning flow and ‘logos’ meaning
science. It is study of the flow or deformation of matter under stress.
Risk management: The systemic application of quality management policies, procedures, and
practices to the tasks of assessing, controlling, communicating and reviewing work.
Roller compaction: A dry granulation process in which a powder blend is passed through
rollers under pressure to form a ribbon .The ribbon is milled into granules, optionally blended
with extra granular excipients and recompressed into tablets or filled into capsules.
Sample thief: Core-type device used to obtain single or multiple samples from different layers
of materials in powder form a large drum or blender.
Saponification value: Number of milligrams of potassium hydroxide needed to saponify one
gram of fat.
Shelf life (also referred to as expiration dating period): The time period during which a
pharmaceutical product is expected to remain within the approved shelf life specification,
provided that it is stored under the conditions defined on the container label.

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Sieving: It is a technique of shaking and passing a sample through a mesh with holes of a
uniform size. It is a widely used method for measuring particle size distribution.
Site Acceptance Test (SAT): Contractual test (supplier-purchaser) usually performed by
purchaser/user organization.
Small Volume Parenteral (SVP): Parenteral drug packaged in a container of not more 100ml in
volume.
Solute: The substance that dissolves to form ions in solution.
Solution: A solution is a homogenous mixture prepared by dissolving a solid, liquid, or gas in
another liquid.
Specific gravity: Specific gravity is a ratio, expressed decimally, of the weight of a substance to
the weight of a substance to the weight of an equal volume of a substance chosen as a standard,
both substances at the same temperature or the temperature of each being known specific gravity.
Stability: Capability of a formulation in a specific container closure system to remain with in
specifications over a stated time period established to ensure its identity, strength, quantity, and
purity.
Starting material: Any substance of a defined quality used in the production of a
pharmaceutical product, but excluding packaging materials.
Stock solution: It is concentrated solution that may be dilute to some lower concentration for
actual use.
SULPA (Super Ultra-Low Penetration Air): SULPA filters are available where maximum
cleanliness is required. These filters have an efficiency of 99.9999% on the same basis as ULPA
filters.
Superdisintegrants: Swells up to ten fold within 30 seconds when contact water. Example:
crosscarmellose-cross –linked cellulose, crosspovidone-cross-linked povidone (polymer), sodium
starch glycolate-cross linked starch.
Teratogenicity: Teratogenicity is the ability to cause developmental anomalies in a fetus, Things
which can cause developmental abnormalities are known ad teratogens and they include things
like viruses, chemicals, and radiation.
Theoretical yield: The quantity that would be produced at any appropriate phase of
manufacture, processing, or packaging of a particular drug product, based upon quantity of
components to be used, in the absence of any loss or error in actual production.
Tincture: Tinctures are alcoholic or hydro-alcoholic solutions prepared from vegetable materials
or from chemical substances. E.g. paregoric USP, Opium tincture USP.
Topical solutions: Topical solutions are solution, usually aqueous but often containing other
solvents such as alcohol and polyols, intended topical application to the skin. E.g. Hydrogen per
oxide topical solution.

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Total Parenteral Nutrition (TPN): Method of administrating life shaving or life maintain
nutrition by intravenous methods to patients unable to take nutrition properly.
Traceability: A prerequisite for trustworthy records, apart from data security. Traceability is the
part of the laboratory data system audit trail that hold the evidence of who did what to a record
and when.
Tranquilizer: A drug used to suppress an acute disturbed emotional state. E.g. Trifluoperazine.
Troches: Troches are solid dosage forms in the form of small disk, cylinder, or tablets, intended
to be placed in the mouth and allowed to dissolve or disintegrant.
T- test: Statistical test used hypotheses about the mean of a random population, as well as
hypotheses about the mean difference between two independent random populations.
U-chart: The u-chart is a type of control chart used to monitor ‘count type’ data where the
sample size is greater than one typically the average number of nonconformities per unit. Where
u is the symbol that represents the number of nonconformance in a single sample.
ULPA: ULPA is an acronym for “Ultra-Low Penetration Air” . ULPA may also be used to refer
to Ultra-Low Particulate Air. A ULPA filter can remove from the air at least 99.999% of dust,
pollen, mold, bacteria, and any airborne particles with a size of 120 nanometers (0.12) or larger.
Ultraviolet (UV) radiation: Electromagnetic spectrum with a wavelength of about 200 to 4000
nanometers. Absorbance of UV light can be used for quantitative analysis of drug.
Uniformity: A staring material may be considered uniform when samples drawn from different
layers do not show significant differences in the quality control tests, which would result in non-
conformity with specifications.
Universal antidote: An antidote used in poisoning where specific antidote is not available. It
consisted of two parts of activated charcoal, one part of tannic acid and one part of magnesium
oxide.
Unit doe container: Single unit container for drugs intended for administration by other than the
parenteral route as a single dose directly from the container.
U.S.P (united states pharmacopeia): An official compendium of testing and purity criteria for
pharmacological, ancillaries, and raw materials. It is recognize in Federal food, Drug and
Cosmetic Act Serves Administration involving official drugs. It is published every five years by
the United States Pharmacopeial Convention, a nonprofit organization.
Vaccine: A vaccine is a biological preparation that provides active acquired immunity to a
particular disease
Validation master plan: VMP is a high level document that establishes an umbrella validation
plan for the entire project and summarizes the manufactures overall philosophy and approach, to
be used for establishing performance adequacy.

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Validation protocol: A written plan describing the process to be validated, including production
equipment and how validation will be conducted. Such a plan would address objective test
parameters, product and process characteristics, predetermined specifications, and factors, which
will determine acceptable results.
Vendor: A person or an organization that provides any products or documentation to the user for
a fee or in exchange for services. Such a firm could be a medical device manufacture.
Veterinary: Referring to pharmaceuticals or biological intended for animal use. Historically
veterinary products were made by less than “Good Manufacturing Product”. Today, however, the
GMP’s refer to both human and veterinary products.
Warning letter: Issued by the FDA after inspection to an organization that is not compliance
according to FDA’s definitions. The organization will normally first receive a ‘483’ and will
have to answer they plan to do with the problems found by the inspectors. If answer is not
satisfactory, the FDA will issue a warning letter.
Water number: Maximum amount of water that can be added to 100 grams of an absorption
base at a given temperature.
Working solution: It is a solution which is ready for use. This solution is usually prepared from
stock solution before analytical use.
World Trade Organization (WTO): Established on 1 January 1995 as the successor to GATT.
While GATT was applied on a ‘provisional basis’, WTO commitments are full and permanent
for the entire membership. Three councils have been set up by the WTO to oversee trade in the
flowing areas: goods, service and trade related aspects of intellectual property rights.
Worst case: A set of conditions encompassing upper and lower processing limits and
circumstances, including those within standard operating procedures, which pose the greatest
chance of process or product failure when compared to ideal conditions. Such conditions do not
necessarily induce product or process failure.
Yield Value: Finite force necessary before a rheological flow can start.
Zeta potentials: It is defined as the difference in potential between the surfaces of the tightly
bound layer and the electro-neutral region of the bulk phase. It is the charge or potential existing
at the surface of a particle. It is the positive charge measured at the surface of the membrane
across the pH range.
Z-value: Temperature difference that causes a 10-fold change in D value (time to destroy 90%
of the microorganisms under described condition).

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 Chapter- Fourteen

Pharmaceutical abbreviation

Important Abbreviations
A
AAA Abdominal Aortic Aneurysm
A-a Alveolar To Arterial Gradient
gradient
AAD Antibiotic-Associated Diarrhea
AAO Alert, awake, and Oriented
A &O Alert & Oriented
AAS Acute Abdominal series/Atomic Absorption Spectroscopy
ABD Abdomen
ABG Arterial Blood Gas
AC Before Eating
ACLS Advanced cardiac Life support
ACTH Adrenocorticotropic Hormone
ADH Anti-Diuretic Hormone
ADR Adverse Drug Reaction/Acute dystonic Reaction
Ad lib As much as needed
AED Antiepileptic Drug
AF Atrial fibrillation or Afebrile
AFB Acid-Fast Bacilli
AFB Alpha-Fetoprotein
A/G Albumin/Globulin ratio
AI Aortic Insufficiency
AkA Above The knee Amputation
ALD Alcoholic liver Disease
ALL Acute Lymphocytic Leukemia
Amb Ambulate
AML Acute Myelogenous leukemia
ANA Antinuclear Antibody
ANS Autonomic Nervous System
AOB Alcohol on Breath
AODM Adult Onset Diabetes Mellitus
AP Anteroposterior or abdominal- perineal
ARDS Acute Respiratory Distress Syndrome
ARF Acute Renal failure
AS Aortic Stenosis
ASAP As soon as possible
ASCVD Atherosclerotic cardiovascular Disease

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ASD Atrial Septal Defect
ASHD Atherosclerotic Heart Disease
AV Atrioventricular
A-V Arteriovenous
A-V 02 Arteriovenous oxygen

B
BBB Bundle Branch
BCAA Branched Chain Amino Acids
BE Barium Enema
BEE Basal Energy Expenditure
BID Bis in Die(twice a day)
BKA Below The Knee amputation
BM Bone Marrow or Bowel Movement
BMR Basic metabolic Rate
BOM Bilateral Otitis media
BP Blood Pressure
BPH Benign Prostatic Hypertrophy
BPM Beats Per Minute
BRBPR Bright Red Blood Per Rectum
BRP Bathroom Privileges
BS Bowel or Breath Sounds
BUN Blood Urea Nitrogen
BX Biopsy

C
C&S Culture and Sensitivity
CA Cancer
Ca Calcium
CAA Crystalline Amino Acids
CABG Coronary Artery
CAD Coronary Artery Disease
CAT Computerized Axial Tomography
CBC Complete Blood count
CC Chief Complaint
CCU Clean Catch Urine or Cardiac Care Unit
CCV Critical Closing Volume
CGL Chronic Granulocytic Leukemia
CGMP Current Good Manufacturing Practices

CHF Congestive Heart Failure

CHO Carbohydrate
CI Cardiac Index
CML Chronic Myelogenous Leukemia
CMV Cytomegalovirus
CNS Central Nervous System

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COA Certificate of Analysis
CO Cardiac Output
COLD Chronic Obstructive lung Disease
COPD Chronic Obstructive Pulmonary Disease
CP Chest Pain or Cerebral Palsy
CPAP Continuous Positive Airway Pressure
CPK Creatine
CPR Cardiopulmonary Resuscitation
CRCL Creatinine Clearance
CRF Chronic Renal Failure
CRP C-Reactive Protein
CSF Cerebrospinal Fluid
CT Computerized Tomography
CVA Cerebrovascular Accident or Costovertebral Angle
CVAT Cva Tenderness
CVP Central Venous Pressure
CXR Chest X-Ray

D
DAT Diet As Tolerated
DAW Dispense As Written
DC Discontinue or Discharge
D& C Dilation and Curettage
DDX Different Diagnosis
D5W 5% dextrose in Water
DI Diabetes insipidus
DIC Disseminated Intravascular Coagulopathy
DIP Distal Interphalangeal joint
DJD Degenerative Joint Disease
DKA Diabetic Ketoacidosis
dL Deciliter
DM Diabetes mellitus
DNR Do not Resuscitate
DOA Dead on Arrival
DOE Dyspnea on Exertion
DPL Diagnostic Peritoneal Lavage
DPT Diphtheria, Pertussis, Tetanus
DVT Deep Venous Thrombosis
DX Diagnosis

331
 E
EAA Essential Amino Acids
EBL Estimated Blood Loss
ECG Electrocardiogram
ECT Electroconvulsive Therapy
EFAD Essential Fatty Acid Deficiency
EMG Electromyogram
EMV Eyes, Motor, Verbal, Response
ENT Ears, Nose, and Throat
EOM Extraocular Muscles
ETP Effluent Treatment Plant
ET Endotracheal
ETT Endotracheal Tube
ERCP Endoscopic Retrograde Cholangio
Pancreatography
ETOH Ethanol
EUA Examination under Anesthesia

F
FBS FASTING Blood Sugar
EB Foreign Body
FDA Food and Drug Administration
FEV Forced Expiratory Volume
FFP Fresh frozen Plasma
FRC Functional residual Capacity
FTT Failure To Thrive
FU Follow Up
FUO Fever of Unknown Origin
FVC Forced Vital Capacity
Fx Fracture
FBS Fasting Food Sugar
FEV Forced Expiratory Volume
FRC Functional Residual Capacity
FIFO First in
First out
FTT Failure to Thrive
FU Follow up
FUO Fever of unknown Origin

G
GB Gallbladder

332
GC Gonorrhea
GERD Gastroesophageal Reflux Disease
GFR Glomerular Filtration Rate
GETT General by Endotracheal Tube
GLP Good Laboratory Practice
GRN Goods Received Note
GFR Glomerular
Filtration Rate
GIT Gastrointestinal Tract
GSW Gun Shot Wound
GTT Glucose Tolerance Test
GU Genitourinary
GXT Graded Exercise Tolerance
Gt or gtt Drops

H
HA Headache
HAA Hepatitis B Surface Antigen
HAV Hepatitis A Virus
HBV Hepatitis B Virus
HCV Hepatitis C Virus
HBP High Blood Pressure
HCG Human Chorionic Gonadotropin
HCT Hematocrit
HDL High Density Lipoprotein
HEENT Head, Eyes, Ears, Nose, Throat
Hgb Hemoglobin
H/H Henderson-Hasselbalch Equation or Hemoglobin
Hematocrit
HIV Human immunodeficiency Virus
HLA Histocompatibility Locus Antigen
HJR Hepatojugular Reflux
HOB Head of Bed
HPF High Power Field
HPI History of Present Illness
HPLC High Performance Liquid chromatography
HR Heart Rate
HS At Bedtime
HSM Hepatosplenomegaly
HTLV-3 Human Lymphotropic Virus, type 3
HSV Herpes Simplex Virus
HTN Hypertension
HVAC Heating ventilating Air Conditioning
Hx History

333
 I
I&D Incision and Drainage
I&O Intake and Output
ICS Intercostal Space
ICU Intensive Care Unit
ID Infection Disease or Identification
IDDM Insulin Dependent Diabetes Mellitus
IG Immunoglobulin
IHSS Idiopathic Hypertrophic Subaortic Stenosis
IM Intramuscular
IMV Intermittent Mandatory Ventilation
INN International Nonproprietary Name
INF Intravenous Nutritional Fluid
IPPB Intermittent Positive Pressure Breathing
IRBBB Incomplete Right Bundle Branch Block
ISO International Standard Organization
IRDM Insulin Resistant Diabetes Mellitus
IT Intrathecal
ITP Idiopathic Thrombocytopenic Purpura
IV Intravenous
IVC Intravenous Cholangiogram/Inferior Vena Cava
IVP Intravenous Pyelogram

J
JODM Juvenile Onset Diabetes Mellitus
JVD Jugular Venous Distention

K
KOR Keep Open Rate
KUB Kidneys, Ureters, Bladder
KVO Keep Vein open

L
L Left
LAD Left Axis Deviation or Left Anterior Descending
LOD Loss on Drying
LAE Left Atrial Enlargement
LAL Test Limulus Amebocyte Lysate test
LAHB Left Anterior Hemiblock
LAP Left Atrial Pressure
LBBB Left Bundle Branch Block
LD50 Lethal dose 50%
LDH Lactate Dehydrogenase
LIFO Last in first out

334
LLL Left Lower Lobe
LMP Last Menstrual Period
LNMP Las Normal Menstrual Period
LOC Loss of Consciousness or Level of
Consciousness
LP Lumbar Puncture
LPN Licensed Practical Nurse
LUL Left Upper Lobe
LUQ Left Upper Quadrant
LV Left Ventricle
LVEDP Left Ventricular End Diastolic Pressure
LVH Left Ventricular Hypertrophy

M
MAO Monoamine Oxidase
MAP Mean Arterial Pressure
MAST Medical Antishock Trousers
MBT Maternal Blood Type
MCH Mean Cell Hemoglobin
MCHC Mean Cell Hemoglobin Concentration
MCV Mean Cell Volume
MI Myocardial Infarction
MIC Minimum Inhibitory Concentration
mL Milliliter
MLE Midline Episiotomy
MMEF Maximal Mid Expiratory Flow
mmol Millimole
MMR Measles, Mumps, Rubella
MRI Magnetic Resonance Imaging
MRSA Methicillin Resistant Staph Aureus
MS Multiple Sclerosis
MSSA Methicillin Sensitive Staph Aureus
MVI Multivitamin Injection
MVV Maximum Voluntary Ventilation

N
NAD No Active Disease
NAS No Added Salt
NCV Nerve Conduction Velocity
NED No Evidence of Recurrent Disease
ng Nanogram
NG Nasogastric
NIDDM Non-insulin Dependent Diabetes Mellitus
NKA No Known Allergies
NKDA No Known Drug Allergies

335
NMR Nuclear Magnetic Resonance
NPO Nothing by Mouth
NRM No Regular Medications
NSR Normal Sinus Rhythm
NT Nasotracheal
NSAID Non-Steroidal Anti Inflammatory Drugs

O
OB Obstetrics
OCG Oral Cholecystogram
OT Occupational Therapy
OD Over Dose or Right Eye
OM Otitis media
OOB Out of Bed
OOP Out of Plaster
OPV Oral Polio Vaccine
OR Operating Room
OS Left Eye
OU Both Eyes

P
P Para
PA Posteroanterior
PAO2 Peripheral Arterial Oxygen Content
PAP Pulmonary Artery Pressure
PAT Paroxysmal Atrial Tachycardia
P & PD Percussion and Postural Drainage
PC After Eating
PCWP Pulmonary Capillary Wedge Pressure
PDA Patent Ductus Arteriosus
PDR Physicians Desk Reference
PE Pulmonary Embolus
PEEP Positive End Expiratory Pressure
PFT Pulmonary Function Tests
Pg Picogram
PI Pulmonary Insufficiency Disease
PKU Phenylketonuria
PM Packaging Materials
PMH Previous Medical History
PMI Point of Maximal impulse
PMN Polymorphonuclear Leukocyte
PND Paroxysmal Nocturnal Dyspnea
PO By Mouth
POD Post of Day
PP Postprandial or Pulsus Paradoxus

336
PPD Purified protein Derivative
PR By Rectum
PRBC Packed Red Blood Cells
PRN As Needed
PS Pulmonic Stenosis
PT Prothrombin Time
Pt Patient
PTCA Percutaneous Transluminal Coronary
Angioplasty
PTH Parathyroid Hormone
PTT Partial Thromboplastin Time
PUD Peptic Ulcer Disease
PVC Premature Ventricular Contraction
PVD Peripheral Vascular Disease
PTHC Percutaneous Transhepatic Cholangiogram

Q
q Every (E.G. Q6h=Every 6 hours)
qd Every Day
qh Every Hour
q4
h Every 4 hours
q6h Every 6 Hours
qid Quarter in Die (latin) Four times a day
QNS Quantity not sufficient
qod Every Other Day
Qs/Qt Shunt Fraction
Qt Total Cardiac Output

R
R Right
RA Rheumatoid Arthritis or Right Atrium
RAD Right Atrial Axis Deviation
RAE Right Atrial Enlargement
RAP Right Atrial Pressure
RBBB Right Bundle Branch Block
RBC Red Blood Cell
RH Relative Humidity

RDA Recommended Daily Allowance

RDW Red Cell Distribution Width
RIA Radioimmunoassay
R&D Research and Development
RIH Right Inguinal Hernia
RLL Right lower Lobe
RLQ Right lower Quadrant
RML Right Middle Lobe
RNA Ribonucleic Acid

337
R/O Rule out
ROM Range of Motion
ROS Review Of System
RPG Retrograde Pyelogram
RRR Regular Rate and Rhythm
RT Respiratory Or Radiation Therapy
RTA Renal tubular Acidosis
RTC Return to Clinic
RU Resin uptake
RUG Retrograde Urethrogram
RUL Right Upper lobe
RV Residual Volume
RVH Right Ventricular Hypertrophy
Rx Treatment

S
s Without
SA Sinoatrial
SAA Synthetic Amino Acid
S&E Sugar And Acetone
SBE Subacute Bacterial Endocarditis
SBFT Small Bowel Follow Through
SBS Short Bowel Syndrome
SCr Serum Creatinine
SEM Systolic Ejection Murmur
SG Swan-Ganz
SGA Small For Gestational Age
SGGT Serum Gamma Glutamyl Transpeptidase
SGOT Serum Glutamic Oxaloacetic Transaminase
SGPT Serum Glutamic pyruvic Transaminase
SIDAH Syndrome of inappropriate Antidiuretic
Hormone
sig Write on Level
SIMV Synchronous Intermittent Mandatory Ventilation
SLE Systemic Lupus Erythematosus
SMO Slips Made out
SOAP Subjective, Objective, Assessment, Plan
SOB Shortness of Breath
SOP Standard operating Procedure
SQ Subcutaneous
STAT Immediately
SVD Spontaneous Vaginal Delivery
Sx Symptoms

338
T
T&C Type and Cross
TAH Total Abdominal Hysterectomy
T&H Type and Hold
TB Tuberculosis
TBG Total Binding Globulin
T4 Thyroxin
T3 Tri-idothyronine
TENS Transcutaneous Electrical Nerve Stimulation
Td Tetanus-Diphtheria Toxoid
TIA Transient Ischemic Attack
TIBC Total Iron Binding Capacity
tid Three times a day
TIG Tetanus Immune Globulin
TMS Tetramethyl Silane
TMJ Temporomandibular Joint
TNTC Too Numerous to Count
TO Telephone order
TOPV Trivalent Oral Polio Vaccine
TPN Total Parenteral Nutrition
TQM Total Quality Management
TSH Thyroid Stimulating Hormone
TT Thrombin Time
TTP Thrombotic Thrombocytopenic purpura
TU Tuberculin Units
TUR Transurethral resection
TURBT Tur Bladder Tumors
TURP Transurethral Resection of Prostate
TV Tidal Volume
TVH Total Vaginal Hysterectomy
tw Twice A Week
Tx Treatment, Transplant

U
UA Urinalysis
UAc Uric Acid
UBD Upper Blood Donor
UC Ulcerative Colitis
ud As Directed
UFH Unfractionated Heparin
UGI Upper Gastrointestinal
URI Upper Respiratory Infection

339
URQ Upper right Quadrant
US Ultrasound
UTI Urinary Tract Infection
UUN Urinary Urea Nitrogen
UVA Ultraviolet A Light

V
VAD Venous Access device
VC Vital Capacity
VCT Venous Clotting Time
VCUG Voiding Cystourethrogram
VDRL Venereal Disease Research Laboratory
VMA Vanillylmandelic Acid
VO Verbal or Voice Order
V/Q Ventilation Perfusion
VRE Vancomycin Resistant Enterococcus
VSS Vital Signs Stable
VT Ventricular Tachycardia
VV Varicose Veins
VW Vessel Wall
VWD Von Willebrand's Disease
VZV Varicella Zoster virus

W
WB Whole Blood
WBC White Blood Cell
WBR Whole Body Radiation
WD Well Developed
WF White Female
WFI Water For injection
WIA Wounded in Action
WID Widow
WM White Male
WN Well Nourished
WNL Within Normal Limits
WO Written Order
WOP Without Pain
W.P. Whirlpool
WPW Wolf Parkinson White
W-T-D Wet to Dry
W/U Work up

340
X
X2d Times 2 Days
XL Extended Release
XM Cross Match
XMM Xeromammography
XOM Extra Ocular movements
XS Excessive
XULN Times Upper Limit Of Normal

Y
YF Yellow Fever
YLC Youngest Living Child
yo Years Old
YOB Years Of Birth
yr Year
ytd Year to Date

Z
ZDV Zidovudine
ZE Zollinger Ellison
Z-ESR Zeta Erythrocyte Sedimentation Rate
Zn Zinc
Zno Zinc Oxide
ZSB Zero Stools Since Birth

341
 Chapter- Fifteen

List of essential drugs

Sl. Name of drugs Dosage form

1 Abacavir (ABC) Oral liquid, Tablet
2 Acetazolamide Tablet
3 Acetylsalicylic acid Suppository, Tablet
4 Acyclovir Powder for injection, Tablet
5 Albendazole Tablet (chewable)
6 Allopurinol Tablet
7 Aluminium hydroxide + Magnesium Oral liquid, Tablet
hydroxide
8 Amitriptyline Tablet
9 Amlodipine Besylate Tablet
10 Amoxicillin Capsule or Tablet, Powder for oral liquid, Powder for
injection
11 Ampicillin Powder for injection
12 Anti-immunoglobulin (human) Injection
13 Antitetanus immunoglobulin (human) Injection
14 Artemether + Lumefantrine Tablet
15 Artesunate Injection, Tablet
16 Ascorbic acid Tablet
17 Atenolol Tablet
18 Atropine Injection, Solution (eye drops)
19 Barium Sulfate Aqueous suspension
20 BCG vaccine Injection
21 Benzathine benzylpenicillin Powder for injection
22 Benzoic acid + Salicylic acid Ointment or cream
23 Benzyl benzoate Lotion
24 Benzyl penicillin Powder for injection
25 Betamethasone Ointment or cream
26 Bleomycin Powder for injection
27 Bupivacaine Injection
28 Calcium gluconate Injection
29 Carbamazepine Oral liquid, Tablet (chewable), Tablet (scored)
30 Charcoal, activated Powder
31 Chlorambucil Tablet
32 Chloramphenicol Eye drops, Eye ointment
33 Chlorhexidine Solution
34 Chloroquine Oral liquid, Tablet
35 Chlorpheniramine Injection, Tablet
36 Chlorpromazine Injection, Oral liquid, Tablet
37 Ciprofloxacin Tablet or powder for suspension
38 Cisplatin Injection

342
39 Clofazimine Capsule
40 Clotrimazole Vaginal cream, Vaginal tablet
41 Cloxacillin Capsule, Powder for injection, Powder for oral liquid.
42 Condoms
43 Cyclophosphamide Powder for injection , Tablet
44 Dapson Tablet
45 Dexamethasone Injection
46 Dextran 70 Injectable solution
47 Diazepam Injectable, Tablet, Tablet (scored)
48 Didanosine Buffered powder for oral liquid, Capsule (unbuffered
enteric coated), Tablet (buffered chewable,
dispersible)
49 Diethylcarbamazine Tablet
50 Digoxin Injection, Oral liquid, Tablet
51 Diloxanide Tablet
52 Diphtheria antitoxin Injection
53 Diphtheria vaccine Injection
54 Dopamine Injection
55 Doxorubicin Powder for injection
56 Doxycycline Capsule or Tablet, Tablet (dispersible)
57 DPT vaccine Oral + Injection
58 Efavirenze (EFV or EFZ) Capsule, Oral liquid, Tablet
59 Enalapril Tablet
60 Epinephrine (adrenaline) Injection, Solution (eye drops)
61 Ergocalciferol Capsule or Tablet, Oral liquid
62 Ergometrine Injection
63 Erythromycin Capsule or Tablet, Powder for in injection, Powder
for oral liquid
64 Ethambutol Tablet
65 Ethinylestradiol + Levonorgestrel Tablet
66 Ferrous salt Oral liquid, Tablet
67 Ferrous salt + Folic acid Capsule, Tablet
68 Fluconazole Capsule, Oral liquid
69 Fluorescein Eye drops
70 Fluorouracil Injection, Ointment
71 Fluphenazine Injection
72 Folic acid Tablet
73 Furosemide Injection, Tablet
74 Gentamycin Injection. Solution (eye drops)
75 Gentamycin + Hydrocortisone Ear drop
76 Glibenclamide Tablet
77 Gliclazide Tablet
78 Glucose Injectable solution
79 Glucose with sodium chloride Injectable solution
80 Glyceryl trinitrate Tablet (sublingual)
81 Griseofulvin Capsule or Tablet
82 Haloperidol Injection, Tablet
83 Halothane Inhalation
84 Heparin sodium Injection

343
85 Hepatitis B vaccine Injection
86 Homatropine Solution (eye drops)
87 Human normal immunoglobulin Intramuscular administration, Intravenous
administration
88 Hydrochlorothiazide Tablet (scored)
89 Hydrocortisone Powder for injection, Ointment or cream,
Suppository
90 Hyoscine butylbromide Tablet, Injection
91 Ibuprofen Tablet
92 Indinavir (IDV) Capsule
93 Insulin injection (soluble) Injection
94 Isoniazide Tablet, Tablet (scored)
95 Isoniazide + Ethambutol Tablet
96 Isosorbide dinitrate Tablet (sublingual)
97 Ketamine Injection
98 Lamivudine (3TC) Oral liquid, Tablet
99 Levamisole Tablet
100 Levodopa + Carbidopa Tablet
101 Levothyroxine Tablet
102 Lidocaine Injection, Topical
103 Lithium Carbonate Capsule or Tablet
104 Lopinavir + Ritonavir (LPV/r) Capsule, Oral liquid
105 Magnesium hydroxide Oral liquid
106 Magnesium sulfate∗ Injection
107 Mannitol Injectable solution
108 Measles vaccine Injection
109 Mebendazole Tablet (chewable)
110 Mefloquine Tablet
111 Metformin Powder for injection, Tablet
112 Methotrexate Powder for injection, Tablet
113 Methyldopa Tablet: 250 mg
114 Methylrosanilinium chloride (gentian Aqueous solution, Tincture
violet)
115 Metoclopramide Injection, Tablet
116 Metronidazole Injection, Oral liquid, Suppository, Tablet
117 Miconazole Ointment/ Cream
118 Miltefosine Capsule/ Oral liquid
119 Misoprostol Tablet
120 Morphine Injection, Oral liquid, Tablet, Tablet (prolonged
release)
121 Naloxone Injection
122 Nelfinavir (NFV) Oral powder , Tablet
123 Neomycin Sulfate +Bacitracin Ointment
124 Neostigmine Injection, Tablet
125 Nevirapine (NVP) Oral liquid, Tablet
126 Nicotinamide Tablet
127 Nifedipine Immediate release capsule
128 Nitrofurantoin Tablet
129 Nitrous oxide Inhalation

344
130 Nystatin Oral Suspension
131 Omeprazole Capsule
132 Oral rehydration salts Powder
133 Oseltamivir Tablet
134 Oxygen Inhalation
135 Oxytocin Injection
136 Paracetamol Oral liquid, Suppository, Tablet
137 Paromomycin Solution for intramuscular injection
138 Peritoneal Dialysis Solution Intraperitoneal dialysis solution (of appropriate
composition)
139 Permethrin Cream, Lotion
140 Pertussis vaccine Injection
141 Pethidine hydrochloride Injection
142 Phenobarbital Injection, Oral liquid, Tablet
143 phenoxymethylpenicillin Powder for oral liquid, Tablet
144 Phenytoin Capsule, Injection, Oral liquid, Tablet, Tablet
(chewable)
145 Pilocarpine Solution (eye drops)
146 Poliomyelitis vaccine Oral
147 Polyvalent anti snake venom Injection
148 Potassium chloride Tablet, Solution
149 Povidone Iodine Solution
150 Prednisolone Tablet, Solution (eye drops)
151 Primaquine Tablet
152 Procainamide Injection
153 Procaine benzylpenicillin Powder for injection
154 Procarbazine Capsule
155 Proguanil Tablet
156 Promethazine Oral liquid, Injection, Oral liquid, Tablet
157 Propranolol Tablet
158 Protamine sulfate Injection
159 Pyrazinamide Tablet, Tablet (dispersible), Tablet (scored)
160 Pyridoxine Tablet
161 Pyrimethamine Tablet
162 Quinine Injection, Tablet
163 Rabies immunoglobulin Injection
164 Rabies vaccine Injection
165 Retinol Capsule, Tablet, Oral oily solution, Water-miscible
injection
166 Riboflavin Tablet
167 Rifampicin Capsule or Tablet
168 Rifampicin + Isoniazid Tablet
169 Rifampicin + Isoniazid+Ethambutol Tablet
170 Rifampicin+Isoniazid+Pyrazinamide Tablet
171 Rifampicin+Isoniazid+Pyrazinamide+ Tablet
Ethambutol
172 Ritonavir Oral liquid, Oral solid dosage form
173 Salbutamol Injection, Oral liquid, Respiration solution for use in
nebulizers, Tablet

345
174 Salicylic acid Solution
175 Saquinavir (SQV) Capsule
176 Senna Tablet
177 Silver sulfadiazine Cream
178 Sodium chloride Injectable solution
179 Sodium chloride 3% I/V fluid
180 Sodium chloride quarter strength I/V fluid
(0.225%)
181 Sodium Hydrogen Carbonate Injectable solution, Solution
182 Sodium stibogluconate Injection
183 Sodium thiosulfate Solution
184 Spironolactone Tablet
185 Stavudine (d4t) Capsule, Powder for oral liquid
186 Streptomycin Powder for injection
187 Sulfadoxine+Pyrimethamine Tablet
188 Sulfamethoxazole + Trimethoprim Oral liquid, Tablet, Injection
189 Suxamethonium Injection, Powder for injection
190 Tamoxifen Tablet
191 Tenofovir disoproxil fumarate (TDF) Tablet
192 Tetanus vaccine Injection
193 Tetracycline Eye ointment
194 Thiamine Tablet
195 Thiopental Powder for injection
196 Trimethoprim Tablet
197 Tropicamide Eye drops
198 Tuberculin, purified protein Injection
derivative (PPD)
199 Valproic acid Oral liquid, Tablet (crushable), Tablet (enteric
coated)
200 Vecuronium Injection
201 Verapamil Injection, Tablet
202 Vinblastine Powder for injection
203 Vincristine Powder for injection
204 Vitamin B-Complex (Vitamin B1 – Tablet
5mg +vitamin B2- 2mg + vitamin B6
– 2mg +Nicotinamide 20mg
205 Warfarin Tablet
206 Water for injection Ampoule
207 Xylometazoline Hydrochloride Nasal drops
208 Zidovudine (ZDV or AZT) Capsule, Oral liquid, Solution for IV infusion
injection, Tablet oral liquid, Tablet
209 Zinc sulphate Oral liquid, Tablet

346
 Chapter- Sixteen

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