PROCESSING OF PARENTERAL PREPARATION
The following steps are involved in the processing of parenteral preparation:
1. Cleaning of containers, closures, and equipment.
2. Collection of materials.
3. Preparation of parenteral products.
4. Filtration.
5. Fill the preparation in the final container.
6. Sealing the container.
7. Sterilization
8. Evaluation of the parenteral preparation.
9. Labelling and packaging.
1. Cleaning of containers, closures, and equipment: Thoroughly cleaned with detergents with tap water distilled water finally rinsed with water for injection. Rubber closures are washed with 0.5% sodium pyrophosphate in water.
2. Collection of materials: All raw materials of preparation should be collected from the warehouse after accurate weighing. Water for injection should be Pyrogens-free.
3. Preparation of parenteral products: The Parenteral preparation must be prepared in aseptic conditions. The ingredients are accurately weighed separately and dissolved in the vehicle as per the method of preparation to be followed.
4. Filtration: The Parenteral preparation must be filtered by a bacteria-proof filter such as a filter candle, or membrane filter.
5. Filling the preparation in the final container: The filling operation is carried out under strict aseptic precautions.
6. Sealing the container: Sealing should be done immediate after filling in aseptic environment.
7. Sterilization: For thermostable substances, the Parenteral products are sterilized by autoclaving method at different temperature and pressure. E.g. 10 lb pressure (115.5oC, or 240oF) for 30 minutes, 15 lb pressure (121.5oC, or 250oF ) for 20 minutes, 20 lb pressure (126.5oC, or 260oF) for 15 minutes. Heat sensitive or moisture sensitive materials 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:
• Sterility test
• Clarity test
• Leakage test
• Pyrogen test
• Assay
9. Labelling & packaging
Evaluation of Parenteral Products
• Sterility testing
• Particulate matter monitoring
• Faculty seal packaging or leakage test
• Pyrogens testing
• LAL test
• Assay or drug content uniformity .
Sterility testing:
Definition: It is a procedure carried out to detect and conform absence of any viable form of microbes in or on pharmacopeia preparation or product.
Principle: Sterility testing only shows that organisms capable of growing in selected conditions are absent from the fraction of batch that has been tested. If the microorganism are present in the product can be indicated by a turbidity in the clear medium.
Objectives 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 involved in Sterility Testing
• Sampling
• Selection of the quantity of the product to be used
• Methods of sterility testing:
(i) Method 1: Membrane filtration method
(ii) Method 2: Direct inoculation method
• Observation and interpretation must be carried out under aseptic condition.
1. Sampling: The sample must be representative of the whole of the bulk material and a lot of final containers.
It is mainly followed by two rules:
• A fixed percentage of the final container are selected.
• A fixed number of containers are taken independent of the lot or batch size.
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.
3. Methods of sterility testing :
(i) Membrane filtration method (Method 1):
• Membrane filtration method is appropriate for :
o Filterable aqueous preparations
o Alcoholic preparations
o Oily preparations
o Preparations miscible with or soluble in aqueous or oily (solvents with no antimicrobial effect.
• All steps of this procedure are performed aseptically in a Class 100 Laminar Flow Hood.
Membrane filter 0.45 μ porosity, Filter the test solution. After filtration remove the filter.
Cut the filter in to two halves. First half (for Bacteria) and Second half (for fungi), Transfer in 100 ml culture media (Fluid Thioglycollate medium).
Incubate at 30-35oC for not less than 7 days. Transfer in 100 ml culture media (Soyabeans-Casein Digest medium). Again incubate at 20-25oC for not less than 7 days. Observe the growth in the media.
(ii) Direct inoculation method (Method 2):
• Suitable for samples with small volumes.
• Volume of the product is not more than 10% of the volume of the medium.
• Suitable method for aqueous solution, oily liquids, ointments and creams.
• Suitable quantity of the preparation to be examined is transferred directly into the appropriate culture medium and incubate for not less than 14 days.
Observation and results:
Culture media is examined during and after at the end of incubation.
The following observations are possible:
• No evidence of growth pass the test for sterility.
• There is evidence of growth re-testing is performed same number of sample, volume and media as in original test. No evidence of growth pass the test for sterility.
• There is evidence of growth isolate and identify the organism. Re-testing is performed with twice number of sample if: No evidence of growth pass the test for sterility. There is evidence of growth Fail the test for sterility.
