Quality Control Tests for

Parenteral
• Parenteral preparations are sterile preparations
intended for administration by injection,
infusion, or implantation into the human body
or animal body.
• Parenteral preparations must be sterile
• free of microorganisms
• To ensure sterility, parenterals are prepared
using
– aseptic techniques
– special clothing (gowns, masks, hair net, gloves)
– laminar flow hoods placed in special rooms
• Advantages and Disadvantages
 Advantages
• Rapid onset of action
• Administrable to nonresponsive patients
• Patient convenience and comfort
• Administrable directly to site of action
• Better absorption
Parenteral Routes of Administration

1. Intra-articular 6. Intrasynovial
–joints –joint fluid
2. Intracisternal 7. Intrathecal
–spinal fluid
3. Intra-arterial 8. Intracardiac
–arteries –heart
4. Intravenous 9. Intramuscular
–veins –muscles
5. Intradermal 10. Subcutaneous
–skin –under the skin
GENERAL REQUIREMENTS OF PARENTERAL
PREPARATIONS

• Stability
• Sterility
• Free from Pyrogens
• Free from foreign particles
• Isotonicity
• Specific gravity
• Chemical purity
 Official Types of Injections
1. Drug Injection
- Liquid preparations that are drugs substances or
solutions thereof.
Example: Insulin Injection, USP

2. Drug for Injection

- Dry solids that, upon the addition of suitable
vehicles, yield solutions conforming in all
respects to the requirement for Injections
Example: Cefamandole Sodium for
Injection
 Official Types of Injections

3. Drug Injectable Emulsion

- Liquid preparations of drug substances
dissolved or dispersed in a suitable
emulsion medium
Example: Lipofundin
Official Types of Injections
4. Drug Injectable Suspension
- Liquid preparations of solids suspended in a
suitable liquid medium
Example: Methylprednisolone Acetate
Suspension

5. Drug Injectable for Suspension

- Dry solids that, upon the preparations conforming
in all respects to the requirements for Injectable
Suspensions
Example: Imipenem + Cilastatin for Injection
Suspension, (Tienem)
Factors affecting Stability
1- Environmental factors
- Temperature - Light
- Oxygen - Moisture
- Carbon dioxide

2- Drugs or excipients in the dosage form

- Particle size of drug
- pH of the vehicle

3- Microbial contamination .
 Processing of parenteral
preparations
• 1. Cleaning of containers, closures & equipment’s: Thoroughly
cleaned with detergents, with tap water, distilled water finally rinsed
with water for injection. Rubber closures are washed with 0.5% sod.
Pyrophosphate in water.
• 2. Collection of materials: All raw material of preparation should
be collected from warehouse after accurate weighing. Water for
injection should be Pyrogen free.
• 3. Preparation of parenteral products: The parenteral
preparation must be prepared in aseptic conditions. The ingredients
are accurately weighed separately and dissolved in vehicle as per
method of preparation to be followed.
• 4. Filtration: The parenteral preparation must be filtered by
bacteria proof filter such as, filter candle, membrane filter.
• 5. Filling the preparation in final container: The filling operation
is carried out under strict aseptic precautions.
• 6. Sealing the container: Sealing should be done immediately after
filling in aseptic environment.
• 7. Sterilization: For thermo stable substances the
parenteral products are sterilized by autoclaving method at
different temp. & pressure.
• 10 lb. pressure (115.50C, or 2400F) for 30 minutes
• 15 lb. pressure (121.50C, or 2500F ) for 20 minutes
• 20 lb. pressure (126.50C, or 2600F) for 15 minutes
• Heat sensitive or moisture sensitive material are
sterilized by exposure to ethylene oxide or propylene oxide
gas .
• 8. Evaluation of the parenteral preparation: The
following tests are performed in order to maintain quality
control:
• 1. Sterility test 2. Clarity test 3. Leakers
test
• 4. Pyrogen test 5. Assay for active ingredients
• 9. Labeling & packaging .
 Sterility Test
• It is a procedure carried out to detect and
confirm the absence of any viable form of
microbes in pharmacopeial preparation or
product.
• OBJECTIVE OF STERILITY TESTING:
• For validation of sterilization process.
• To check presence of microorganisms in
preparation which are sterile.
• To prevent issue of contaminated product in
market.
Steps
1. Sampling
• The sample must be representative of the whole of the bulk material
& a lot of final containers.
Number Of Items In the Batch
• Not more than 100 containers
• More than 100 but not more than
500 containers
• More than 500 containers
Minimum Number of Items
Recommended to be tested
• 10% or 4 container whichever is
greater
• 10 containers
• 2% or 20 containers (10
containers for LVP) whichever is
less
2. Selection of the quantity of the product to be used
• Selection of the quantity of the product to be used for sterility testing
depends mainly on the volume or weight in the container

Quantity of Each Container Minimum Quantity to be Used For Each

Culture Medium
• FOR LIQUIDS
• ≤ 1 ml • The whole contents of the container.
• > 1ml – 40 ml • Half of the contents of the container
but not less than 1 ml.
• > 40ml and ≤ 100 ml • 20 ml
• >100ml • 10 % of the contents of the container
but not less than 20 ml.
FOR SOLIDS
• Less than 50 mg • The whole of the contents of the
container
• 50 mg to < 300 mg • Half of the contents of the container
but not less than 50mg
• 300 mg- 5g • 150 mg
• > 5g • 500 mg
 3. Method of sterility testing
• Membrane filtration method (METHOD 1):
• Membrane filtration is Appropriate for :
– Filterable aqueous preparations.
– Alcoholic preparations.
– Oily preparations.
– Preparations miscible with or soluble in aqueous or oily
solvents (solvents with no antimicrobial effect).
• All steps of this procedure are performed aseptically in a Class
100 Laminar Flow Hood.
• Direct Inoculation method ( Method 2):
• In this method suitable quantity of the
preparation to be examined is transferred
directly into an appropriate culture medium so
that the volume of the product is not more than
10% of the volume of the medium, unless
otherwise prescribed
• Incubate for not less than 14 days.
• It is a suitable method for samples with small
volumes.
• It is suitable for oily liquids , ointments and
creams.
• Culture medium is examined during and after the end
of incubation . The following observations are
possible :
– If there is no evidence of growth , pass the test for sterility.
– If there is evidence of growth , test is re-performed using
the same no. or volume of sample and medium as in the
original test.
– Now if there is no evidence of growth , pass the sterility
test for the sample. But if again there is evidence of
microbial growth , retesting is done with twice amount of
the sample and medium. If there is no evidence of growth ,
pass the sterility test and if there is evidence of microbial
growth , the batch is then rejected .