PARENTERAL PREPARATIONS
Definition: Parenteral preparations or injections are the sterile solutions or suspensions
of drugs in aqueous or oily vehicles meant for introduction into the body by means of an
injection under or through one or more layers of the skin or mucus membranes.
They must be sterilised and free from all organisms, toxins and pyrogens, dust and fibres.
They should be isotonic to body fluids.
Routes of administration of parenteral products.
1. Intracutaneous or intradermal injections.
2. Subcutaneous or hypodermic injections.
3. intramuscular injections
4. intraveneous (iv) injections
5. intra arterial injections
Less common routes
6. Intracardiac injections
7. intrathecal injections
8. Intracisternal injections- they are given in between the 1 st and 2nd cervical
vertebrae. This route is used to withdraw CSF for diagnostic purposes.
9. peridural injection
10. intra articular injection
11. intracerebral injection
Advantages of parenteral route
1. The route is used when rapid onset of action is required e.g in emergency.
2. Used when drugs are inactivated in the GIT or are not well absorbed after oral
administration.
3. Used for patients who are not corporative – unconscious or otherwise unable to
take medicine orally
4. prolonged action of drug can be produced by this route
5. Solutions in volumes from a fraction of an ml to litres can be introduced by
parenteral routes.
Disadvantages
1. It is more expensive because it requires a technical and trained person for
administration.
2. Sterilization is of utmost importance.
3. Administration of drug through the wrong route may prove fatal.
4. Frequent administration of injection may pause difficulties.
Types of parenteral preparations
1. Solutions ready for injection
2. suspensions ready for injection
3. emulsions suitable for parenteral administration
4. dry soluble products dissolved in a suitable solvent before administration
5. dry insoluble products which are combined with a soluble vehicle just before
administration
Subcutaneous, intramuscular and IV routes are the most commonly used but the nature of
the product determines the route to be used.
S.C injections should contain water soluble and non – irritiating drugs and should be
isotonic with body fluids to avoid irritation and pain.
For IM injection, the drug may be dissolved or suspended in an aqueous or oily vehicle
but drugs in aqueous vehicles are absorbed faster than drugs in oily solutions or
suspensions in oily vehicles.
Essential qualities of parenteral products
1. It should be free from living – organisms and microbial products
2. Should be free from pyrogens.
3. They should be free from foreign particles e.g dust and fibres
4. free from chemical contaminants
5. should be isotonic with body fluids
6. Should have matching specific gravity with respect to some body fluids.
7. multi-dose injections must contain preservatives
8. Containers/closures must not affect the product.
Formulation of parenteral products
The pharmacist should have thorough knowledge and understanding of the principles
involved and utmost care must be taken regarding accuracy, cleanliness and overall
quality of the product.
Only a minimum number of absolutely necessary additives in smallest possible quantities
should be added.
Some of the additives used in the formulation of parenterals include:
Vehicle
A suitable vehicle is used for dissolving or suspending the medicament. The most
suitable vehicle is water because equeous preparations are tolerated well by the body and
are the safest and easiest to administer.
The water should be chemically pure and pyrogen free.
When water free from dissolved gases is required, it should be freshly boiled, cooled and
stored in a well closed container to avoid absorpotion of O2 and CO2.
Oily vehicle is used when water is contraindicated e.g
i. when the medicament is insoluble in water.
ii. To increase the stability of the preparation
iii. To prolong the duration of action of drug
The commonly used fixed oils from vegetable origin are – cotton seed oil, sesame oil,
peanut oil, olive oil.
These oils should be free from rancid odour and taste.
NOTE: Mineral oils are not used because they are not absorbed from the tissue after
injection.
Other additives
1. Solubilizing agents: - The solubilities of insoluble or poorly soluble drugs in water
can be increased by:
- Co-solvents
- Complex formation
- By adding surfactants like tweens and polysorbates which act by micellar
solubilization.
2. Stabilizers – oxidation and hydrolysis take place more rapidly in drugs when they are
in solution form.
To prevent oxidation, a suitable antioxidant is added or the product is sealed in an
atmosphere of nitrogen or carbon dioxide so as to replace O 2 in the product thus
minimizing oxidation.
Hydrolysis can be prevented by replacing part or whole of water in the preparation by
a non aqueous vehicle or by adjusting the pH of the preparation.
3. Buffers: When the degradation of the preparation is due to change in pH, it is
prevented by adding buffer systems which maintain the necessary pH at the desired
level.
Acetates, citrates, phosphates are the principle buffer system.
4. Antibacterial agents: - Bacteriostatic or fungistatic agents must be present in
multidose containers. They prevent the multiplication of organisms that may be
accidentally introduced when withdrawing a dose from a mutlidose container.
They include:
Benzalkonium chloride 0.01%
Phenol or cresol 0.5%
Chlorocresol 0.2%
Phenyl mercuric nitrate 0.002%
Chlorobutanol 0.5%
The agents should be compatible with all other components of the solution and should not
be removed from the solution by rubber closures of the package.
Bacteriostatic agents should not be used in single dose containers because the contents
remain sterile until the solution is opened.
5. Isotonicity factors: - Parenteral preparations must be isotonic with blood serum and
other fluids to reduce the irritation and pain of injection in areas with nerve endings.
Isotonicity is adjusted by adding sodium chloride in suitable quantities.
6. Wetting, suspending and emulsifying agents
A wetting agent is used to reduce the interfacial energy between the solid particles and
the liquid so as to prevent the formation of lumps.
They also act as antifoaming agents to subside the foam produced during shaking of the
preparation.
The wetting agents commonly used and tween 80 and sorbitan trioleate.
Suspending agents used:
- Methyl celulose
- Carboxymethyl cellulose
- Acacia
- Gelatin.
Emulsifying agents – used in sterile emulsion. Lecithin is generally used.
Gelatin may be added to aqueous vehicles to prolong the effect of the drug.
General Procedure for Preparation of Injections.
All parenterals must be free from foreign particles and organisms.
Care must be taken regarding cleanliness and sterilization of the area, atmosphere,
persons involved and the materials used in the preparation of injections.
The area and the atmosphere of the room must be free from dust, fibres and
microorganisms. This is achieved with a laminar air flow or with disinfectants.
- All equipment must be thoroughly cleaned and sterilized.
- The workers should be highly trained and skilled.
- They should wear sterilized special clothings including hoods and gloves.
Parenterals should be prepared from substances of high purity that have been accurately
weighed and dissolved in oxygen free disstileld water or any other suitable solvent.
The solution formed is passed through different grades of filters to remove foreign
particles. The filters are made from sintered glass, asbestos or porcelain.
Bacteria-proof filters are used to remove bacteria from solutions.
The solution is packaged in suitable containers like ampules, vials or bottles that have
been thoroughly cleaned, dried and sterilized.
The closures used should be of very high quality and must be sterilized.
- On a small scale, filling is carried out with the help of a hypodermic syringe
attached with a long needle or burette.
- The sealing of the ampule is done by fusion of glass in hot flames of a blast
burner or a blow torch specially designed for this purpose.
Currently, filling and sealing is done on very sophisticated automatic machines.
Sterilization and validation
After filling and sealing the containers are sterilized by means of dry heat or moist heat.
For dry heat sterilization, hot air ovens are used
For moist heat sterilization, autoclaves are used.
Oily and non-aqueous preparations must be sterilized by dry heat at a temp of 160 0 for
2hrs or 1700c for 1 hr.
Thermostable aqueous solutions are sterilized by steam under pressure in an autoclave at
a temp of 1210c for 20 min.
Aqueous solutions of thermo-labile drugs cannot be sterilized by autoclaving. They are
passed through bacteria – proof filters to remove microbes.
The sterilized containers are allowed to cool and are inspected for clarity. Containers that
pass the clarity test are properly labeled and packaged into final containers.
Precautions for Aseptic Work to Prevent Contamination.
1. Only a minimum number of persons should work in the injection department.
The lesser the number of persons the lesser the contamination.
2. Only persons trained in aseptic techniques should be allowed in the injection
department.
3. Before entering the sterile area – personnel must wash their hands and should then
be treated with antiseptic solutions, wear gloves, change dresses, cover hair, wear
face mask and a hood over the head.
The clothes worn must not shed fiber or other particles.
4. The air must be free from contaminants- This is ensured by a laminar air flow in
the areas.
5. U.V lamps should be fitted above the roofs, working tables and room ceilings.
6. Walls should be painted so as to allow easy cleaning, washing and disinfection.
7. There should be minimum hide outs
8. Furniture should be minimum and fitted with stainless steel or other suitable
surfaces.
9. Double door entry should be provided
10. There should be a minimum number of windows that must be kept closed
11. Equipment must be thoroughly cleaned and sterilized before and after use.
12. Frequent tests should be performed in the aseptic area to check the maintenance
of sterility
13. When contamination is detected, the source should be identified and suitable
methods used to check the contamination.
I.V fluids / Large Volume Parenterals.
They are solutions administered IV to supply body fluids, electrolytes and to provide
nutrition to the body.
They are administered in volumes of 250ml to a number of litres per day by IV drip.
They must be free from pyrogens. Since they are administered at one time, they don’t
contain bacteriostatic agents or other additives.
They are packaged in single dose glass or plastic containers. Example:
i. Dextrose injection – it contains 2.5% 5%; 20 or 50% dextrose. They are used
as a fluid and nutrient replenishers.
ii. Dextrose and NaCl injection – it contains dextrose from 2.5 – 25% and 0.11-
0.9%NaCl. It is used as a nutrient and electrolyte replenishers.
iii. Fructose injection – contains 10% fructose and is used as a fluid and nutrient
replenisher.
iv. Mannitol injection – it contains 5, 10, 15, 20, 25% mannitol and is used as a
diagnostic aid in renal function determinations and as diuretic.
v. Ringer’s injection – it contains 0.86% NaCl- 0.03 KCl-, 0.033% CaCl. It is
used as an electrolyte replenisher.
vi. Lactated ringer solution ( ringer lactate) – it contains 2-7 Meq of calcium, 4
meq of pottasion and 130meq of Na and 2.45g lactate per litre. The solution
is used as a systemic alkalinizer, a fluid and electrolyte replenisher.
vii. NaCl injection (Normal saline) Contains 0.9% Nacl. It’s used as a fluid and
electrolyte replenisher. It is also used as an isotonic vehicle.
viii. IV Fluids are used as maintainance therapy for patients who undergo surgery
or for unconcious patients unable to take fluids and nutrition orally.
They are also used as replacement therapy for patients who have suffered heavy loss of
fluids and electrolytes e.g vomiting and diorrhoea.
Total Parenteral Nutrition/-HYPERALIMENTATION
This is the infusion of large volumes of basic nutrients sufficient to produce active tissue
synthesis and growth. The solutions contain high concentration of dextrose (20%)
electrolytes, vitamins and proteins.
The solutions are administered slowly through a large vein near the heart for rapid
dilution of the concentrated hyperliamatation fluid so as to minimize the risk of tissue or
cellular damage due to hypertonicity of the solution.
Effect of incorporating drugs into infusion bottles
Nurses incorporate drugs like antibiotics vitamins, etc into large volume parenterals by
injecting the drug through the rubber closure.
This may be dangerous because it may lead to:
1. Bacterial growth as no infusion contains a bactericide.
2. The sugars are good medium for bacterial growth
3. The added drugs may lead to interactions between the drugs. Additives may
result in certain visible changes e.g haziness, precipitation, crystallization, and
discolouration or may affect the efficiency or potency of the drug.
The pharmacy staff should have thorough knowledge about the physical and chemical
compatibilities of the additives in which the solution is placed.
He/she should discourage the addition of medicament to bottles of infusion.
Irrigation and Dialysis Solution
Irrigation and dialysis solutions are similar to parenteral solutions.
They are not injected into the vein and are used outside the circulatory system. Irrigation
solutions are used for washing wounds, surgical incisions or body tissues.
They include:
Ringer irrigation USP
NaCl irrigation USP
Sterile water for irrigation USP
Dialysis is a process by which substances are separated from one another due to their
difference in diffusibility through membranes.
Dialysis solutions are used e.g in poisoning or kidney failure or kidney transplant.
In renal failure, removal of waste products and the maintenance of electrolyte balance are
done either by hemodialysis or intraperitonial dialysis.
Student’s assignment
Read on haemodialysis and intraperitonial dialysis.
Evaluation of parenteral preparations
Student’s assignment:
Read on the following tests and write short notes:
Sterility test
Pyrogen test
Clarity test
Leaker test
Isotonic solutions
All injectables should be isotonic e.g ophthalmic solutions should be isotonic with
lachrymal fluids to prevent irritation and pain.
Injectables should be isotonic to blood plasma
For adjustment of injectable solutions, substance like NaCl or dextrose is added.
0.9% NaCl is isotonic, 0.45% NaCl is hypotonic, 6% is hypertonic.
Packaging of Parenteral Products
The package must be neat and attractive to convey to the user quality, purity and
reliability of the product.
The package should protect the product from physical damage during transport, handling
and storage. Light sensitive products should be protected from UV light.
Containers and closures for injectables must not interact physically or chemically with
the preparation to preserve the effectiveness.
Glass must be of high quality – clear, colourless or light amber colour to permit the
inspection of the contents. Products sensitive to alkalis should be packed in neutral glass.
Injections are packed either in single dose of multi-does containers.
Trends in Packaging
- Parenterals are packed in ampules, vials and transfusion bottles. In ampules,
when the glass is broken, fragments may enter the content and contaminate it.
- In vials and transfusion bottles the problem may arise due to rubber that may
absorb some contents.
The trends include:-
i. A special kind of vial known as mix-o-vial is used for packing sterile powder
and their vehicles or for packing incompatible drugs. This vial has two
compartments (upper and lower compartment)
The lower chamber contains the dry ingredient and the upper contains the liquid
diluent. The two compartments and separated by a special centre seal.
To use the vial, pressure is applied on the top plunger with the help of the thumb that
dislodges the centre seal and allows the liquid to flow into the lower chamber.
The vial is shaken until a solution is obtained
The solution is withdrawn by inserting a syringe needle.
Advantages
1. They offer stability ot the products
2. They are convenient
3. They offer safety as the right drug is mixed with proper diluent and in correct
proportions.
ii. Pre-filled disposable syringes
A new technique of packaging parental products.
