The document discusses the formulation of parenteral preparations, emphasizing their sterile nature, production processes, environmental control, and sterilization methods. It outlines the importance of maintaining aseptic conditions during production and details various sterilization techniques such as autoclaving, filtration, and dry heat sterilization. Additionally, it describes the types of containers used, highlighting the advantages of glass and plastic containers, as well as the role of rubber closures in preventing contamination.

1. DEPARTMENT OF PHARMACEUTICAL SCIENCES
DR. HARISINGH GOUR VISHWAVIDYALAYA
SAGAR (M.P.)
FORMULATION OF PARENTERAL
SUBMITTED BY-
Neetesh Ahirwar
M. Pharm. 1st sem

2. CONTENT-
 Definition
 Production
 Environmental control
 Processing
 Sterilization
 Containers
 Closers
 References

3. DEFINITION-
These are the sterile preparation intended to administered other
than intestinal route to bypass first pass metabolism and directly
goes to systemic circulation.
• These preparation give quick onset of action and site specific
activity.
• Suitable for drugs which are inactive in GIT environment.
• Can be given unconscious or vomiting or diarrheal patient.

4. PRODUCTION-
The production process includes all of the steps from the
accumulation and combining of the ingredients of the formula to
the enclosing of the product in the individual container for
distribution.
• Whole operation perform under SOP.

5. FACILITIES IN PRODUCTION AREA-
• ceiling, wall and floor should be generally constructed of
ceramic epoxy finish which is easy to clean, non- porous,
prevent moisture and debris accumulation
• Glass is often use to supervisory view of operation.
• Careful planning of mechanical servicing of electrical, gases,
water and air ventilation.
• Laminar air flow design should be there.

7. ENVIRONMENTAL CONTROL-
The standards of environmental vary, depending on the area
involve (clean up, packaging, compounding, filling) and the type
of product being prepared.
• Traffic control
• Air control
• surface disinfection
• personnel

8. TRAFFIC CONTROL-
• Carefully design arrangement to control and minimize traffic
particularly in and out of aseptic area is essential.
• The workers who enter the aseptic area, these should not
permitted to move in and out of area before completion of
process.
• Unauthorized personnel should never be permit to enter the
aseptic area.
• Access by personnel to aseptic corridor and aseptic
compounding and filling area is only through the air lock
system.

9. AIR CONTROL-
• Air is the greatest source of contamination so air must be
exchange at frequent intervals.
• Fresh outside or recycled air must be filter to remove
particulate matter so spun glass, cloth, shredded, polyethylene
filter may be use as prefilter.
• To remove finer debris include microorganism, high
efficiency particulate air filter (HEPA) is used.

10. HEPA FILTER-
• It is at least 99.97% efficient in removing particles of 0.3 micro
meter size and larger.
• Composed of glass (borosilicate) fibres and fillers or electrostatic
precipitators.
• Air passing through these units can be free from foreign matter.
• Blowers should be installed in the air ventilation system
upstream to the filters so that all dirt producing devices are ahead
of the filters.
• HEPA filter installed at the point where the clean area enter in
control room.

11. • Efficacy of HEPA filter is evaluated by dioctyl phthalate
test(DOP test).
• Laminar air flow has greatly improved the potential for
environment control of aseptic area.
• The air velocity in laminar air flow system is 80-120ft/min.

13. TYPE OF LAMINAR AIR FLOW SYSTEM-
 Vertical flow system
 Horizontal flow system
 Wall to floor system

14. 1. VERTICAL FLOW SYSTEM-
• This system consist of false floor and ceiling.
• The air is filter through prefilters, electrostatic filters and
HEPA filter in sequence and all are placed in false ceiling.
• From the false floor a small portion of filtered is recirculated
into false ceiling through a recirculating duct.
• It is more preferred compare to horizontal flow system.
• It is expensive as it require double installation of HEPA
filter.

16. 2. HORIZONTAL FLOW SYSTEM-
• The air is filter through prefilters, HEPA filters which are
placed in lateral walls.
• Air is recirculated through punched plate wall and
recirculating duct.
• Achievement of complete sterile condition is not possible
because the air flow is not focused on working area.

18. 3. WALL TO FLOOR FLOW SYSTEM-
• The filtered air enters from lateral walls within inclined flow
towards the flow.
• In this system working area is offered with high aseptic
condition.
• This system is expensive.

20. PROCESSING-

21. 1. CLEANING EQUIPMENT AND CONTAINERS-
• Equipment and containers to be used in the processing of sterile
products must be clean.
• Unused containers and equipment are contaminated principally
with dust, fibers, and chemical film which usually ease to
remove by rinsing only.
• After cleaning the equipment should be rinsed several times,
with a final rinse with WFI.
• Cleaning is accomplished primarily with high pressure rinsing
treatment delivered automatically.

22. 2. STERILIZATION OF EQUIPMENT-
• In general equipment, containers, closers and all other
components should be sterilized after cleaning and prior to use.
• Dry heat sterilization and moist heat sterilization are used for
sterilization of equipment.
• Stainless steel equipment are also sterilize by gas sterilization.

23. 3. COMPOUNDING THE PRODUCT-
• The product should be compounded under clean environmental
conditions.
• Large tank, equipment and ingredients should be sterile to
reduce the microbial load.
• In large batches, particular attention must be given to achieving
homogeneity of solutions, suspensions, and mixtures
maintaining a given temperature and accelerating cooling.

24. 4. FILTRATION OF SOLUTIONS-
• The primary object of filtration are clarification or sterilization
of solution.
• It must be filtered through bacteria proof filter such as
membrane filters and sintered glass filters.
• After the filtration, the solution must be protected form
environmental contamination until it is sealed.
• The filtrate is fed directly from the collecting vessel to filling
machine through sterile hose connections.

25. 5. FILLING PROCEDURE IN AMPULES/VIAL-
• The filtered product is filled into ampules or vials with the
help of semi-automatic or automatic machine under aseptic
condition.
• Sterility is maintained by using laminar air flow benches
which provide clean air.

27. 6. SEALING-
• Sealing should be done immediately after filling under
aseptic condition. Sealing of ampoules is done by two
method
i. Tip sealing- the tip of ampule is melted and heat is
provided from all sides. melting of glass will form a bead
and does close the opening.
ii. Pull sealing- ampule below the tip is melted and rotated
uniformly. As the glass has melted the tip of the ampule is
pulled.
• Vials and bottles are sealed by fitting the rubber closer with
the help of vacuum and then aluminium caps are further
placed on it.

29. STERILIZATION OF PARENTERAL FORMULATION-
 Sterilization is done by various methods depending upon nature
of preparation .
 sterilization of parenteral is carried out by-
 moist heat sterilization or autoclaving
 Sterilization by filtration
 Dry heat sterilization

30. 1. AUTOCLAVING-
 Microorganisms can be killed using boiling water and steam
at pressure higher than atmospheric pressure.
 Formulation is generally sterilize in autoclave at 15 pound at
121degree centigrade for 15 minutes or 10 pound psi at 115
degree centigrade for 30 minutes.
 this method is use for sterilization of injection solutions and
suspension.
 This method also use for sterilization of glass apparatus,
containers closers, and plastic screw caps.

31. 1. STERILIZATION BY FILTRATION-
• In this method all living and dead bacteria get removed when the
solution is filtered through bacteria proof filtration media.
• These filters function by pores which are formed by fusion of
porcelain, sintered glass, metal, cellulosic or plastic polymer
matrix.
• Various filter media are used for bacteria proof filtration-
 Sintered ceramics
 Fibrous pad
 Sintered glass
 Microporous plastic.

32. 3. DRY HEAT STERILIZATION-
• This method is of particular value in
case of oily injections.
• Drugs which are stable at 150
centigrade and thermostable.
• Sterilization by dry heat is usually
carried out in an hot air oven.
• It is a metallic chamber made up of
steel or aluminium.

33. CONTAINERS-
1. GLASS CONTAINER-
• For parenteral preparation mainly for SVP, glass containers
are more preferred.
• In pharmaceutical, soda lime and borosilicate glass are used.
• Most resistant glass is mainly composed of SIO2.
• Boric oxide sometime used to soften the glass.
• Glass containers coated internally with silicon fluid, to
produce hydrophobic surface.
• Powder glass test and water attack test are used for testing of
glass.

34. TYPE OF GLASS CONTAINERS-

35. 2. PLASTIC CONTAINER-
• Plastic container are use mainly because they are light in
weight, non-breakable, low toxicity and low reactivity with
product.
• The principle ingredient of various plastic materials used for
container is thermoplastic polymer.
• Polypropylene is most widely used because it has high
tensile strength, high melting point of 165 centigrade,
relatively low permeable to gases.
• Polyethylene polymer are also used because translucent and
aggressive resistant.

36. material Autoclaving
ability
Gas permeation
capacity
Water vapour
permeation
capacity
low density
polyethylene
no low high
High density
polyethylene
yes low low
polypropylene yes low high
PVC yes low high
Poly amide(nylon) yes low high
polystyrene no high high

37. CLOSERS-
• Rubber closer most commonly used to permit introduction of
needle from a hypodermic syringe to a multiple dose vials and
single dose type preparation.
• Rubber closer composed of multiple ingredients mixed
together at elevated temperature in milling machine.
• Teflon coating used for lining of rubber closer or area which is
in contact with liquid, which decrease the chance of interaction
of any component of formulation with rubber closer as well as
decrease chance of leaching.

38. REFERENCES-
 Lachman Leon, Lieberman Herbert A., “The theory and
practice of industrial pharmacy”, special Indian edition 2009,
CBS publishers and distributors PVT. LTD. New Delhi,
India.

39. THANK YOU