Abstract

The main objective of this project is to the facilitate the basic concept of
parenteral preparation, area planning, general requirements, formulation of
parenteral preparation, evaluation of parenteral preparation. Parenteral
preparation gives quick onset of action so it is useful in emergency cases.
Compare to other dosage forms parenteral preparation are efficient .Typically a
sterile drug contains no viable microorganisms and is non-pyrogenic. Drugs for
intravenous injection for irrigation and those used as ophthalmic preparations
meet these criteria. In addition, other dosage forms might be labelled as sterile,
for instance an ointment applied to a puncture wound or skin abrasion.
 INTRODUCTION
Parenteral is non-enteral or non-oral and therefore strictly the term parenteral
include all products introduction other than oral rout.
As the parenteral (Greek: Para - beside, enteron - intestine) dosage form are
directly injected in body tissue through skin and mucous membrane therefore
parenteral dosage form differ from all other drug dosage form. Parenteral
dosage form should be pure and free from biological, physical and chemical
contaminants, because of these requirements pharmaceutical industry face a
heavy responsibility to goods manufacturing practices (cGMPs) in
manufacturing of parenteral dosage form .
Those pharmaceutical product which are given by other than oral routes are
parenteral preparation, example: Transfusion fluids and injections. Injections
are sterile solution in aqueous or oily vehicle which is introduced into the body
by using injectable needle in one or more layer of the skin and mucous
membrane. Injections must be free from foreign particles like dust and fibres,
they should also be sterile and isotonic. Injections administered through the
suitable route for which they are prescribed, for example oily suspension meant
for intramuscular injection may be very dangerous if it is given by intravenous .
The most common routes through which the parenteral is introduced are
intravenous, subcutaneous, and intramuscular route, the variety of lesser used
route like intra-arterial. In addition, products usually classed as parenteral, are
subcutaneous implants.
The drugs which are being given by injections are preferred to be prepared by
simple solutions in water but can also said as aqueous suspension, oily solution
and even emulsions. Although some drugs are unstable in solution and these are
dispensed as dry solids in ampoules or multi-dose containers, in which a sterile
vehicle is quickly added.
 CHARACTERISTICS OF PARENTERAL PREPARATION

 Parenteral preparation must be sterile.

 Parenteral product must be free from pyrogenic contamination or foreign
particle , and visible particulate matter.
 Parenteral preparation are chemically, physically and microbiologically stable
(fibres, dust etc.)
 Parenteral product isotonic with body fluid. Isotonicity is depends on route of
administration (Product administered in to cerebrospinal fluid must be
isotonic).
 Sterility maintain during use or storage of parenteral suspension.
 Size of parenteral suspension small and uniform.
 Parenteral suspension is non-irritating or isotonic.
 ADVANTAGES OF PARENTERAL PREPARATION
 Parenteral preparation onset of action is rapid.
 Unconscious patients or unreliable patients
 Certain parenteral preparation provide prolong drug action e.g. penicillin G
provide action up to a month when administered intramuscular route.
 Parenteral route is sutiable for irritant drug and high first pass.
 Parenteral preparation is use in emergency cases because onset of action is
fast such as epilepsy, asthma etc.
 DISADVANTAGES OF PARENTERAL PREPARATION
 Injection causes pain at the site of administration of drug or local irritation as
a result of needle insertion.
 High cost of production.
 They can not easily be self administration. Trained persons are required to
administered the drug.
 Administration of drug through wrong route of injection may prove to be fatal.
 In case drug is overdose it is difficult to save a patients.
 There are chances of allergic reaction of a drug by individual. These reactions
are very fatal and lead to death.
 They required aseptic condition or follow proper aseptic technique during
manufacturing.
 It poses more risks than the other route .
 ROUTE OF ADMINISTRATION OF
PARENTERAL PREPARATION
1. Intradermal Injection (Intracutaneous)

Injection Intradermal injection is given in between dermis and epidermis.

Left forearm of skin selected giving injection. 0.1 to 0.2 ml of parenteral
preparation injected this route.

Figure: Intradermal Injection

 Uses: For diagnostic tests such as susceptibility to certain bacterial diseases

such as Tuberculosis, administration of BCG Vaccine.
2. Subcutaneous Injection (Hypodermis)
The drug injected into subcutaneous tissues beneath the dermis into upper
arm of thigh or lower part of abdomen. Not more than 1ml volume inject
because limited subcutaneous area. This route is most popular route because
it is convenient for patient or doctor. Example: Insuline prepration, rabies and
cholera vaccine.

Figure: Subcutaneous Injection

 Advantage: As compare to intravenous route risk is minimized. Smooth
absorption over a long period of time.
 Disadvantage: Slower rate of absorption as compare to intravenous and
intramuscular route. Small volume of drug is administered.
3. Intravenous Injection

Injection are given into the vein and introduced into blood steam. Large
volume parenteral from 1 ml to 500 ml injected in this route. Usually select
median basilic vein near anterior surface of the elbow for the administration
because it is easily located and connects with veins of arm.

Figure: Subcutaneous Injection

 Advantage: This route is useful in emergency case because drug is reaches
fast in systemic circulation. Bioavailability is 100%. Large volume parenteral
is given by this route.
 Disadvantage: Introduced only aqueous solution drug by intravenous route.
As the vital organ like heart get exposed overdose of drug administered, thus
this route is maximum risk factor.
4. Intra-arterial Injection

Intra-arterial injection is introduced directly into artery. Intra-arterial

administration is same as intravenous administration excepts that the drug is
administered into artery rather than vein. Intra – arterial administration are
use in treatment of cancer or intravenous access can`t be easily established
like premature infants.
5. Intracardiac Injection

Intracardiac injection is given in to heart muscles and ventricle of heart in

emergency cases only. This route is useful in heart attack or in circulatory
collapse.
6. Intrathecal Injection

Intrathecal injection is use for spinal and lumbar anesthesia. The parenteral
preparation are introduced by puncture between the third and fourth lumbar
vertebrae or given into sub-archnoid space.
7. Intracerebral Injection

This injection are given in to cerebrum.

8. Peridural Injection

Peridural route of administration is useful in spinal anaesthesia or in special

cases. These injection is given between the dura matter and inner aspects of
the vertebra.
9. Intrathecal Injection

Intrathecal injection is injected into the space surrounding the spinal cord.
10. Intra-articular Injection

Intra-articular injection is injected into joint.

 CONTAINER AND CLOSURES USED FOR
PARENTERAL PREPARATION
Containers are made from plastic or glass materials which are used for
parenteral product. The following conditions are required for a container and
closure to be used for parenteral preparation in pharmacopoeia.
 Foreign substance should not yield to the product .
 To make visible the content in it, it should be transparent for inspection.
 No adverse effect should be recognitioned .
1. Glass

For the preparation of containers the following three types of glass are used :-
 Type 1 glass: It is also called as borosilicate glass or resistance glass, it is
mainly used for chemical glass ware, oven ware and container for alkali
sensitive preparation. Silica contain is lessly increase and AlO 2 is
usually present. With BO2 , it is prepared by using Silica and SiO2 .
 Type 2 glass: When the moist SO2 treated with high temperature the soda
lime silicate glass with high hydrolytic resistance is produced. For most acidic
and concentrated liquid preparation the containers which are made from glass
are most suitable.
 Type 3 glass: In this type, there is soda lime silicate glass with only moderate
hydrolytic resistance. From this glass containers are made which are suitable
for non aqueous preparation and powders which are given priority to
administrate immediately.
2. Plastic

Organic polymers which are easily synthetic and can be molded, extruded and
which can be changed into various shape and laminated. Specially for
packaging and also used for making syrings, tubing devices and salines.
 Advantages : They are unbreakable. As they are less in weight, so their cost
of transport is therefore is less. 3.they exist in various size and shape.
 Disadvantage : The common problem is permeation. As it is a plastic
container, atmospheric gaseous vapours or liquid from surrounding environment
enter into the containers. There is also problem for oxidation and hydrolysis.
Also there is leaching problem. Various material used for plastic such as
polyethylene, polypropylene, polyvinylchloride.
3. Rubber Closures

Various type of rubber are used for this purpose for example butyl rubber,
nitrile rubber , silicon rubber etc. because of there low absorption property and
because of low cost then other rubbers butyl rubber is commonly used but it
decomposed above 1300 ⁰C.
 Formulation of Parenteral Preparation
1. Vehicle : Vehicle which are commonly used for the preparation of injections
are :
a. Aqueous Vehicle : Mainly water is used as vehicle majorly, because water is
satisfied well by body and safe to introduced. Most suitable solvent system for
parenterals is sterile water. The The formulation of parenteral preparation need
thorough knowledge of the medicaments and using adjuvants. The thing should
be avoided in parenteral products is the excess used of adjuvants, because some
of them may interfere with drugs.
 Following substances are added to make a stable preparation.
Water, quality used according to monograph like IP, USP, BP. The quality
checked by TDS (Total dissolved solid contents) by gravimetric evaluation. The
aqueous vehicle used are :
i. Water for injection.
ii. Water for injection free from CO.
iii. Water for injection free from dissolved air.
These are the extremely used vehicle in parenteral formulation. Water used for
injection should be free from pyrogen and should have high level of chemical
purity.
According to BP, “the water used for injection can be only prepared by
distillation process.” Water for injection can be prepared by using apparatus
made of glass still which can protect distillate from being contaminated with
pyrogen. The gas which are removed during the preparation of water for
injection are acid or alkaline gases such as 2 and 3, which ensure that water is of
neutral pH.
Products of metabolism of microorganisms are called pyrogen. Pyrogen are
chemically lipid substance which are associated with carrier molecule, usually a
polysaccharide and can may be a peptide. In parenteral and irrigating solution
water used, should be free of pyrogens proper control must be given in
preparation and water storage to achieve it. Pyrogen can be removed from water
by simple distillation process.
b. Non-aqueous Vehicles : Oils and alcohols are commonly used as non-
aqueous vehicles. There are some fixed oils which are used as vehicle are
arachis oil, cotton seed oil, almond oil. When a depot effect is required for a
drug or the medicaments are insoluble or some what soluble in water or the drug
is soluble in oil, then oily vehicle are used generally.
 Properties of non-aqueous vehicle used in Parenteral Preparation
i. Non toxic ,non irritant and inert.
ii. Stable with other ingredients and compactable with them are used.
iii. Should have viscosity to be easily taken out from container and easily
administered.
iv. Non aqueous solvent used are fixed oil , alcohol, and propylene glycol. The
stable parenteral preparation prepared by 40% propylene glycol. 10% alcohol
and water and maintain the pH to 7.
3. Adjuvants /Added Agent : Substance added with API (Active Pharmaceutical
Ingredients) to enhance stability or prevent contamination. Various adjuvants is

used in parenteral preparation such as antifungal agent, buffering agent,

chelating agent, stabilizer etc.
4. Antimicrobial agent : These agent is kill or prevent the growth of micro-
organism. These agent is use in preparation for prevents the growth of
microorganism during storage condition. Antimicrobial agent is added in multi
dose container because of finite probability of accidental contamination during
repeated use. Mostly used antimicrobial agent is used phenylmercuric nitrate,
and benzalkonium chloride.
5. Buffering agent : these agent is use for adjust the pH of the parenteral
preparation. The degradation of the preparation which is due to change in pH.
Avoid this degradation or prevent degradation of preparation added suitable
buffer to maintain pH of the preparation.
7. Antioxidant : This agent maintain the stability of the preparation. Salt of SO 2
include Bi-sulfite, Meta-bisulfite, and sulfite are most common antioxidant used
in aqueous parenteral.
8. Tonicity agent: The solution that are to be injected through intravenous
route, it is important that they should be isotonic are or nearly. So, parenteral
preparation should be isotonic with body fluid. As osmotic pressure changes,
can cause haemolysis of red blood cells to ionic species across red blood cell
membrane, non - isotonic solution particularly if given in quantity greater than
100 ml.
9. Solubilizers : To maintain and stable the aqueous solubility of weak water
soluble drugs, the solubilizers are used. Example - Tweens and polysorbate used
as solubilizers.
10. Chelating agent : very few numbers of chelating agent are been used in
parenteral products such as Disodium EDTA , Citric acid , Tartaric acid, and
some Amino acids are use to serve to complex heavy metal and therefore can
improve the efficacy of antioxidants and preservative. Emulsifying agent are
used in sterile emulsions.
 PRODUCTION FACILITIES
1. Design and Layout for Parenteral Production
Design and Layout for parenteral production shown in fig. In this design, area
such as stock room, cleanup area, preparation area, aseptic area, quarantine area,
finishing and packaging area.

Stock

Fig. Layout Diagram

 Stock Room Area : The area in which the all the raw materials which are to
be manufacture are kept are called as stock room areas. The raw material are
active pharmaceutical ingredients. Excipients like suspending and buffering
agents, solvents , isotonic preparation substance of stabilizers. In order to
maintain stability of raw materials, stock room has a suitable temperature and
humidity also in order to avoid the contamination of products disinfectants
should be treated in room .
 Clean up Area : Clean up area is the area which is kept for cleaning bottles,
vials, ampoules and glass things used for parenteral preparation. The area
should be maintain with suitable temperature and relative humidity. The
suitable temperature should be between 19-230 C, and relative humidity
should be between 45-55%. In the manufacturing of parenteral products the
room should be free from dust, fibers , microorganisms. Construction of clean
up area should be done with stand moisture, steam and detergent.
 Preparation Area : For filling operation, the ingredients which are used in
parenteral products are mixed and prepared in preparation area. It is not
necessary that area should be aseptic but because of strict precaution, one
should take the security that the contamination should not take place outside.
The cabinets and counters should be unspaced and made up of stainless steel so
that after filling no dust should enter.
 Aseptic Filling Area : After preparation area the parenteral formulation is
transferred to aseptic filling area from preparation area. The parenteral
preparation are now filled into containers and finally sealed after filtering it.
The entry in aseptic area for the personal should be through air lock. Well
trained person should be eligible for maintaining sterility in aseptic area. To be
washed or treated with aseptic solution, walls and ceiling of aseptic area should
be sealed and well painted. In aseptic area, the air should be free of dust, fibers
and microorganism. To remove particles from air, the High Efficiency
Particulate Air Filters are used (HEPA), which can remove particles up to 0.3 μ.
► Classification of Clean Room
The relation of class is directly to number of particles per cubic foot of air
equal to or greater than 0.5 μ.
i. Class 100000 : Particle count should not go above the limit of 100000
particles per cubic foot of size 0.5 μ and larger then 700 particle or only 700
particle per foot of size 5.0 μ are larger.
ii. Class 10000 : Particle count should not be go above the limit of 10000
particle per cubic foot of size 0.5 μ and larger or 65-70 particle per cubic foot of
size 5.0 μ and larger.
iii. Class 1000 : Particles count should not go above a total of 1000 particle per
cubic foot of a size 0.5 μ and larger or 10 particle per cubic foot of a size 5.0 μ
and larger.
iv. Class 100 : Particle count should not go above total of 100 particle per cubic
foot of a size of 0.5 μ and larger (2, 14, 15)
 Quarantine Area : After the filling, sealing and sterilization of parenteral
products, the batch is carried up in this area. In the analytical laboratory the
random sample of parenteral products of different batches are kept in this, for
evaluation.
 Finishing and Packaging Area : Labelling and packaging of parenteral
product is done in this area. The proper packaging is necessary to prevent the
parenteral product from damage while transportation. Ampoules should be
packed in partitioned boxes.
2. Environmental Control
The very major concern in potential drug manufacturing is environmental also
there is proof that establishes the relationship between the level of
environmental control and quality of final product.
► Environmental zone grouping – There are the following zones under this -
 Zone 1 : Plant Exterior - The first zone is identified by the plant in it. It can
be control through planning and management. Planning means it includes the
location of a plant that is free of any objectionable air born contaminants.
 Zone 2 : Warehousing : This zone provide minimum protection for product
and material. The openings must be large like (truck, doors etc), this may effect
marginally to insects rodent and birds.
 Zone 3 : This zone is formed by the periphery of the general production area.
All the openings are sealed and large enough opened for material exchanging,
equipment and personal.
 Zone 4 : Clean area - in this zone activities such as washing and preparation
of equipment or accumulation are done .
 Zone 5 : Weighing, Mixing and Transfer Area : Zone 5 only except those
activities which are recommended by cGMP section 21.81 .
 Zone 6 : Filling Area : it is distinct zone of controlled environment area for
an aseptic filling process but for aseptic filling process it may not be distinct
zone .
3. Design Concept of Environmental Control
 Wall and Floor Treatment : Attention of many small of minor details is been
kept by the design of filling area or control environment areas. The requirement
which are basic & are required for the cleanability, that include smooth
cleanable wall, floor, ceiling, fixtures and partition expose columns, wallstuds
and pipes.
 Lighting Fixture : this fixtures with the ceiling should reduce flush. The
diffuser must be sealed integrally using ceiling even though most lighting
fixture are not tightly sealed.
 Change Room : This is the main room which control the all personal access
to all control areas. Layouts of change rooms are from single size rooms to most
rated multi room complexes.
 Personnel Flow : Personnel Flow path should be made for higher level of
cleanliness from zone to zone be such that through change rooms, gowning
areas, locker room and the personnel should be made for cleaner area. This flow
is made for controlling the substance and minimize it accesses. It also control
and maintain traffic in or near working area where the substance which are
control are handle.
 Utility : The unacceptable overhead piping from cleanliness or contamination
because it collect dirt may be difficult cleaning or may leak. The service of
major distribution of utility should be outside of clean area.

PROCESSING OF PARENTRAL PREPARATION

OR PARENTRAL PRODUCT
1. Washing of Container and Closures : The equipment which are necessary
for parenteral preparation are clean with detergents and washing of equipments
such as container, closures are done with tap water, which is followed by clean
distilled water and is used with water for injection. 0.5% of pyrophosphate in
water is used for washing rubber closures with hot solutions. For 2 hr. wash
with soft feed water mixed in 0.5 % Hydrolic acid solution wash with filtered
soft feed water and also with filtered compressed air, after washing pH should
be 6- 7.
2. Collection of Material : The ingredients which are required for formulation
of Parentral preparation are weighed and kept in the room for preparation the
raw materials should be pure which are required for parenteral preparations.
3. Preparation of Parentral Product : As per the manufacturing formula
quantity of each ingredients is weighted accurately. Then it should be transfer
into clean suitable container and stir till dissolved after adding required quantity
of water. Make up the volume with solvent and mix well.
4. Filteration of Solution : Parenteral preparation is filter through Whatmann’s
filter paper or bacteria proof filter such as sintered glass filter. Filtration is
important process to clarify the solution by removing of foreign particle, this
process is done in aseptic condition. Collect the filtrate in suitable sterilized
container and container sealed.
5. Filling and Sealing in Final Container : The filtered product is filled into
final container like vials, ampoules and transfusion bottles. Ampoules filling
used for single dose and vails are multi dose. Filling is done under the laminar
air flow .
6. Seal the Container by Fusion or with appropriate Closures : Ampoules
are sealed manually on small scale by rotating the neck of the ampoules in the
flame of Bunsen burner. The vails and transfusion bottle is sealed with rubber
closure.
7. Sterilization : Sterilization may be defined as the absence of viable
microorganism in pharmaceutical preparation.
►Various sterilization method is used for sterilized parenteral
preparation:
i. Heat Sterilization
ii. Filtration Sterilization.
iii. Ionizing radiation Sterilization.
iv. Gaseous Sterilization.
i. Heat Sterilization
a. Moist Heat Sterilization : Moist heat sterilization is used in 3 form to
achieve microbial inactivation i.e.
(1) Dry Saturated Steam - Autoclave,
(2) Boiling Water at Atmospheric Pressure
(3) Hot Water below Boiling Point.
Moist heat sterilization involves the use of steam in the range of 1210-1340 ⁰C.
For sterilization, steam under pressure is used to generate high temperature.
Steam for sterilization can be eighter wet saturated or dry saturated steam. For
destroy microorganism and sterilization of laboratory glassware, media and
reagent autoclave is use. This method is useful for sterilization of glassware,
dressing , closure etc.
b. Dry Heat Sterilization: in this sterilization method destroyed microorganism
following cellular dehydration and then oxidation. This sterilization process is
carried out in ovens. Heat stable, non aqueous product or powers is sterilized
this method .lower efficiency of dry heat sterilization as compare to moist heat
sterilization, dry heat sterilization is performed at higher temperature and
requires longer time of exposure of the microorganism to this temperature.
Holding temperature is 1800 ⁰C, 1700 ⁰C, 1600 ⁰C for 30 min, 60 min, 120 min
respectively.

ii. Filtration Sterilization

This filtration method is used for thermolabile solution sterilized by filtration
through filters that remove the bacteria. This sterilization method is used for
complete removal of microorganism within specific size range from liquid.
There are two type of filtration mechanism sieving which makes use of
synthetic membrane filters. Adsorption and tapping is second mechanism which
make use depth filters. Generally membrane filter are suitable for removal of
microorganism.
iii. Ionizing Radiation Sterilization
There are 2 main type of radiations i.e., electromagnetic and particulate.
 Electromagnetic Radiation : X-rays, Gamma rays, UV rays etc.
 Particulate Radiation : α-particle and β-particle and neutrons or protons.
Only gamma rays are used for sterilization of pharmaceutical product.
iv. Gaseous Sterilization
Heat sensitive and moisture sensitive material can be sterilized by this method.
8. Evaluation of Parenteral Product : The finished parenteral product are
subjected to the following test ,in order to maintain quality control.
i. Sterility Test - To know the probable sterility of specific batch, the sterility
test is done. The procedural details for sterility testing required is been provided
by USP. The direct method and membrane filtration method are the official test
of USP. To avoid the accidental contamination of product during the test
precaution should be taken that test must be carried out under aseptic condition.
► Various method used for Sterility Test are -
a. Membrane Filtration Method : The method use for filtration of membrane
is membrane filtration. As compare to direct inoculation method, membrane
filtration method requires more knowledge and skill for employmation.
b. Direct Inoculation Method : In this method, two test tube that contain a
culture it involves direct inoculation of sample. Due to repeating the continuous
process of opening container transferring sample and mixing, therefore, this
approach is theoretically easy but technically tough. The sample of test of
parenteral preparation are transfer into test tube which contain the sterile culture
media for anaerobic bacteria and aerobic bacteria and fungi in incubator the test
is incubate for specific period and check the turbidity in sample. If turbidity is
present, it indicates the growth of microorganism and sample is fail to comply
with test for sterility.
ii. Clarity Test - It is a state which is defined as been clear or transparent to
eye. It is a relative subject for well visual acuity, training and experience of
sorter. Only the statement stated in the USP is that all injection should be
subjected to visual inspection, specifications for clarity are not given there.
The product container is inspected by individual human in the presence of good
light baffled against reflection in to the eyes and the product is viewed under a
black and white background in which the contents are set in motion with a
swirling action. If the particle is stationary, it is difficult to recognize then it is
moving, but the care must be taken that air bubbles should not been introduced,
because it is difficult to see them from dust particle. For the light colour particle
the black background is used for detection and for dark particle white
background is used. If any foreign particle is visual in parenteral preparation
this preparation is rejected.
iii. Leakage Test - The Leakage Test is only performed for ampoules by
sealing them from fusion so that the leakage should not occur in them. It
includes 2 sub-test, are -
a. Vacuum Chamber Test – It is the test in which the leakage test is perform.
After dipping the ampoules in 1% solution of Methylene Blue in vacuum
chamber, the vacuum is applied, the solution of colour will enter the ampoules
when vacuum is removed the colour solution with defective sealing. If the
colour solution enter the ampoule it is stated that it is leaked and hence rejected.
Because of flexibility and unmaintance of rubbers, they are not used in this test.
b. Dye Bath Test -
iv. Pyrogen Test - The test which is done to check the absence or present of
pyrogen in liquid parenteral preparation. Pyrogen are produced by
microorganism they are metabolic product of microorganism but maximum
bacteria which are gram negative produced most of pyrogenic substances. They
are polysaccharide and thermostable. They can pass through bacteria proof
filters and also soluble in water they are not affected by bactericide. Principle:
the temperature of rabbit measure also take part in this test. Following
intravenous injection of sterile solution of substance being examined. In this test
rabbits are generally used because there body temperature rises when pyrogen
are administered by parenteral route.
 Material required for Test : Materials such as glasswares, syringes and
needles, temperature recording device. Needle should be wash with water for
injection and raise its temperature on oven at 250 0 C for 30 min. wash the
solution in such away that they should be free from pyrogen and all are sterile.
Three healthy rabbits of any gender male or female each should have a less than
1.5 kg wt. not showing loss of body, complete maintainance of balanced diet.
Do not use any rabbit which is having a temperature above then 39.8 ⁰C.
 Method : The test is carried in air condition room. Substance been examined
in or dilute with pyrogen free saline solution should be dissolved.
Approximately 38.50 ⁰C, before injection the liquid should be examined.
Amount of the sample to be injected varies according to preparation being
examined and prescribed in individual monograph. Volume of injection is not
less than 0.5 ml/kg and not more than 10 ml/kg of body wt.
Clinical thermometer sensing probe is inserted into the rectum of the rabbit for
recording the body temperature. Two normal recording of rectal temperature
should be taken to the test injection at interval of half an hour and its mean
calculate, which is initial temperature recorded for rabbit .
The solution is injected slowly through ear vein in volume of 0.5 to10 ml/kg of
body weight. Temperature is record each rabbit in an interval of 30 min. for
three hours after injection. The difference between initial temperature and
maximum temperature recorded for rabbit is taken its response. When this
difference is negative the result is counted zero response. If the response of an
individual rabbit is less than 0.60 ⁰C, the preparation being examined passes the
test.
9. Labelling and Packaging : After evaluation of the parenteral preparation,
the ampoules, vails and transfusion bottles are properly labelled and packed.
The label should state - name of preparation, quantity of the preparation, Mfg.
Lic. no., batch no., date of manufacture , date of expiry.
 PARENTERAL DRUG DELIVERY SYSTEM
In the area of Parenteral Drug Delivery, various technological advances are
made which are leading to the development of sophisticated system that allow
the targeting and sustained or controlled removal of parenteral medicine. The
offer given by parenteral formulation, particularly intravascular ones is a unique
opportunity for direct access to the blood stream, target to specific organ and
tissue sites and rapid onset of drug action.
► Advantages of Parenteral Drug Delievery System :
i. The Parentral route provide facility and an good way to the patient who are
unconscious and unable to take oral medication.
ii. Quickly therapeutic effect is produced by the drug the administered
parenterally and generally and therefore use in emergency situation.
► Disadvantage of Parenteral Drug Delievery System :
1. The drug if ones injected, it is difficult to reverse it effect .

1. INJECTABLES
These are sterile formulations of drug either in aqueous or oily vehicles that are
administered directly into the systemic circulation by the means of needles amd
syringes. It includes the following -
i. Solutions : For release of parenteral control in drugs, oily and aqueous both
solution are used. Aqueous solution can control the drug released in 3 ways:
1. By increasing viscosity and decreasing molecular diffusion .
2. By forming a complex.
3. By forming complex such as release of drug not by dissociation but by
reducing.
ii. Colloidal Dispersions
 Liposomes : Formation of liposomes are held in aqueous environment by self
assembly of phospholipid molecules. For protecting the hydrophobic groups of
amphiphilic phospholipid they form the closed bilayer sphere for protection
from the aqueous environment.
 Niosomes : Niosomes are obtained by the hydration of synthetic non ionic
surfactants. Niosomes are vesicular system made up of non ionic surfactants.
Without interference of cholesterol or other lipids. The surfactant use for
production of niosomes are non ionic such as sorbitan esters (span series ),
polysorbate (tween series ). They are osmotically active. The drug interapted
increases stability in niosomes. For administration of this the routes are
parenteral as well as topical routes.
 Polymeric Particulate/Micelle : The another innovative parenteral carrier
system are polymeric nano-particle which are prepared for biodegradable
polymers the Parentral sustained released are of many types which are
polymeric microsphere formulation which are been injected intramuscularly or
subcutaneously for systematic injection in specific route .
iii. Nano-particles
 Nano Suspension : The pharmaceutical nano-suspensions are nano-meter
sized drug particle which is disperse finely in an aqueous vehicle for lighter oral
and topical use or pulmonary and parenteral administration. In general the size
of nano suspension is always less than 1 micron and approximately between 100
to 200 nm.
 Nano Emulsion: The liquid dispersion of oil and water that are homogeneous,
transparent and thermodynamically stable by adding surfactant in large amount
and co-surfactant which have the diameter of droplets between 100-1000 nm in
range.
iv. Micro-particles
 Microsphere : Microsphere can be injected by 18 or 20 number needle .
microsphere are freely flowing powder which contain less than 125 micron of
spherical particle size that can be suspended in suitable aqueous vehicle. Each
particle is the matrix of drug which is dispersed in polymer form which release
occurs by first order process. Bio-compatible and biodegradable polymers are
used such as PLA, PLGA, etc. dissolution control the drug release.
 Micro Capsule : The drug is located in the polymeric shell in the center of
finite thickness and dissolution control the release. Quality micro-capsule
release medicaments at the rate of zero also micro-capsules are off thick walls.
⸎ Type A Process - In this the formation of capsule occur in a liquid filled
stired tank or tubular reactor . Example - Complex Coacervation ,
⸎ Type B Process - Formation of capsules in this process are held because the
coating is spread and deposited in such manner that the core material get
dispersed in a gas phase or vacuum. They are deposited on liquid or solid core.
v. Resealed Erythrocyte
The advantages of drug loading into own bodies erythrocytes when it is used to
serve as maintain introducing system.
► Advantages :
1. Fully biodegradable, biocompatible and non immunogenic
2. In circulation, having long life span.
3. The drug is safe from enzymatic inactivation.

2. IMPLANT
Firstly, the concept of implantable therapeutic system for a long term was given
by ‘Lafarge’. According to him,“ the implant technique was use for introducing
crystalline hormone in the form of solid steroid pellets ”. He said ‘this process
can be used for continuous drug administration’. It was introduced in 1861 and
the pellet which was subcutaneous implantable was also developed .
i. In-Situ forming implant
Classification of injectable in-situ forming implants
a. Thermoplastic pastes
b. Thermally induced gelling system
c. In-Situ Polymer Precipitation
ii. Solid Implant :
These devices are implanted by a minor surgical incision of mm and cm
dimension. The devices implant are cylindrical, monolithic. They are also
injected through a large bore needle into the S.C. or I.M. tissue. The easiest way
for implantation, poor perfusion, slow drug absorption, less reactivity is
subcutaneous tissue.

TYPE OF PARENTRAL DEVICES

1. Syringe
These are the things which are used to inject solutions and is a type of sterile
device. To inject or withdraw secretion from the body, the syringes are used.
Syringe is attached to needle. It is a callibrated glass or plastic cylinder.
“Syringe” is the word which is derived from the Greek Syrinx. Many types and
size of syringe are available and which are used for various purposes. Size
varies from 0.25-450 ml.
 Example : Insulin syringe, medical syringe , disposable syringe.
2. Needle
It is a slender, sharp device which is used to inject or for suturing, ligaturing and
puncturing. Also it is used for removal of material in an identified mass by
aspirating it which is clinical through hallow needle attach to syringe. Needle is
reusable ones for single patients and is almost disposable. Needle gauge
indicates the diameter of the needle. Different needle length are available for
different gauge.
 Example : Hypodermic needle , winged needle.
3. Cannulae
The tube inserted into the body for the removal of fluid or to administer it, is
known as cannulae.
4. Catheter
The tube which is inserted in body through the duct or vessel is known as
catheter. It allows injection drainage of fluids by surgical instruments.
Catheterization, is a process of inserting catheter. In most cases, the flexible
and thin catheter is used and larger solid tube catheter is vary.
5. Infusion set
For introducing the fluids from an intravenous container, infusion set is used.
Containing a bottle or bag piercing pin are more basics set found and also a site
chamber for allowing the counting of drops. The container should be situated
higher onto the patient for the solution to flow.
 Uses:
i. use for total Parentral nutrition .
ii. use for blood and blood product.
iii. use for continuous drug theory.
6. Feeding Tube
It is the device which is used for giving nutrition to the patient.

CONCLUSION
The objectives of this review article related to the basic concepts of parenteral
product. It was concluded that the parenteral route of administration is very
effective in emergency cases and very useful in unconscious patients. The
present article describe about the various advantage, disadvantage, production
of parenteral preparation, quality control test or evaluation of parenteral product
and various devices which are used in delievery of the parenteral drugs. We had
known about the various parenteral preparation in the given article.
It is necessary to produce good quality of sterile parenteral product for the
effective use which no complications, side-effects and adverse effects.
Undoubtedly, trained and skilled medical assistance is required for the proper
delievery of the drugs through the parenteral devices to ensure that no
consequences should be appear during the whole process.