Method of preparation of parenteral or processing
Steps of preparation of parenteral:
• Cleaning of container, closure and equipment:
• Sterilization of equipment
• Compounding of material
• Filtration of solutions
• Filling the preparation into final containers
• Sealing of container
• Sterilization of final container
Cleaning of container, closure and equipment:
• New unused containers can be cleaned only by rinsing.
• Previously used containers should be cleaned by using detergents followed by final rinsing with water for injection.
• Containers should be cleaned after disassembling if possible.
• Containers should be used only for one type of product which minimizes the contamination.
• For large tanks, pipes and equipment which can be isolated and placed in a process unit, a special cleaning technique called CIP (cleaning in place) is used.
• Alternative hot and cold water treatment should be used for cleaning the new containers and final washing should be done using Water for injection.
• It can be done using rotary rinser and conveyor type rinser.
• Rubber closures should be washed with hot solution of 0.5% sodium pyrophosphate in water, then washed with water followed by rinsing with water for injection.
Sterilization of containers:
• Containers and equipment are sterilized by autoclaving at 115°c to 116°c for 30 minutes and by hot air oven at 160°c for 2 hours.
Compounding of material:
• All material should be compounded according to the standard given in IP and method of mixing and method of preparation should be decided before compounding.
• The parenteral preparation should be compounded under clean conditions but not essential that compounding area should be aseptic.
Filtration of preparation;
• The compounded solution is filtered through bacteria proof filters, seitz filters, filter candle, and sintered glass filers.
• The objective of filtration is clarification and sterilization.
• Clarification is removal of microbes of at least 0.3µm and sterilization is removal of microbes less than 0.3µm size.
• After filtration the solution must be protected from environmental contamination until it is sealed in final container.
• It can be done by feeding the filtrate from collecting vessel to the filling machine through sterile hose connections.
• A secondary in –line filter is included near the outlet to pick any particulate material from lines and equipment.
Filling in final container:
• The filtered solution is filled into final container like ampoule, vials and transfusion bottles which are previously cleaned and dried.
• Ampoules are used for filling single dose while vials are used for filling multidose.
• Bottles are used for filling transfusion fluids.
• On small scale, filling is done manually by using hypodermic needles and syringes.
• On large scale filling is done by automatic filling machines.
• Solutions are filled into final containers by gravity filling, vacuum filling and pressure filling.
• The sterile powder is filled into final container by individual weighing or by automatic and semi- automatic equipment.
• During filling of ampoule, it should be considered that it should be filled below the neck of the ampoule and solution should not touch the neck of ampoule.
Sealing the containers:
• Sealing should be done in aseptic area adjacent to the filling area.
Sealing is of two types:
• It is done by melting the sufficient glass at the tip of ampoule neck to form a bead and close the opening.
• It is done by heating the neck of a rotating ampoule below the tip and then pulling the tip away to form a small capillary to being melted closed.
• Pull sealing is slower process but it is more reliable than tip sealing.
Sterilization of final container:
• The parenteral preparation after sealing should be sterilized in final container.
• For thermostable substances, the final containers can be sterilized by autoclaving at 115°c – 116°c for 30 minutes or 121°c for 20 minutes and by hot air oven at 160°c for 2 hours.
• Thermolabile substances are sterilized by bacteria- proof filters and it may also contain a suitable bacteriostatic agent to prevent the growth of micro- organism but should not be used if dose is exceeding 15ml and used by IV route.