Module for Grade 9 for Asynchronous/Distance learning
manufacturing of parenterals
1. MANUFACTURE OF SMALL
VOLUME AND LARGE
VOLUME PARENTERALS
PRESENTED BY:
M.SUPRAJA DEEP,
B.PHARMACY,
ST.PETERS INSTITUTE OF
PHARMACEUTICAL SCIENCES.
2. INTRODUCTION :
DEFINITION:
Parenteral preparations are pyrogen-free
preparations intended to be administered other
than oral routes.
The term parenteral is derived from two Greek
words ,
Para outside enteron intestine
CLASSIFICATION:
Based on volume they are classified into two types:
1. Small volume parenterals (SVP’s).
2. Large volume parenterals (LVP’s).
3. SMALL VOLUME PARENTERALS :
The volume is generally less than or equal to
100ml.
They are supplied in single or multiple doses.
They are used to dispense most of the drugs.
4. LARGE VOLUME PARENTERALS :
These are supplied for
single dose having more
than 100 ml.
These are delivered
through IV route.
These generally
provide electrolytes,
nutrition to the body.
8. VEHICLES:
WATER FOR INJECTION(WFI):
water that is intended for use in the
manufacture of parenteral (i.e. injectable) drugs
whose solvent is water.
The USP (United States Pharmacopeia)
defines this as highly purified waters containing
less than 10 CFU/100 ml of Aerobic bacteria.
STERILIZED WATER FOR INJECTION
(SWFI):
sterile, nonpyrogenic, distilled water in a
single dose container for intravenous
administration after addition of a suitable solute.
It may also be used as a dispensing
container for diluent use.
9. .
No antimicrobial or other substance has
been added.
The pH is 5.5 (5.0 to 7.0).
BACTERIOSTATIC WATER FOR
INJECTION (BWFI):
Sterile water containing 0.9% benzyl
alcohol that is used to dilute or dissolve
medications.
The container can be reentered multiple
times (usually by a sterile needle) and the benzyl
alcohol suppresses or stops the growth of most
potentially contaminating.
10. PRETREATMENT OF
WATER:
The water for injection is most commonly used
solvent.
Water for injection is the water prepared by
reverse osmosis or distillation and contains no
added substances.
The water must be adequately pretreated to
ensure the uniformity and to promote constant
quality and high efficiency.
Some of the important elements include:
11. Chlorination or treatment with ozone to suppress
the microbial growth throughout the system.
Prefiltration through depth filters to remove iron
and any suspended matter
Injecting a flocculating agent to remove the
suspending agents, if any.
Water softening by ion-exchange to remove
alkaline earth metals, calcium and magnesium, and
thus minimize the formation of scale deposits.
Ph adjustment to 6.0-6.5 to reduce scale deposits.
Deionization by ion exchange resins to removal of
ions from feed water.
Activated carbon beds for removal of chlorine and
organics and then treatment with UV radiation to
suppress the microbial growth.
12. REVERSE OSMOSIS (RO) :
This is defined as a process for the separation of
solutes from the water by applying pressure on
more concentrated solution in contact with semi
permeable membrane to give less concentrated
solution.
The solutes may be charged (ions) or essentially
neutral (organics) .
Each is excluded or removed by different
mechanisms.
Charged particles are repelled or excluded due to
interfacial tension at the water membrane
iinterface.
14. .
Organics are excluded by sieve mechanism so that
size and molecular weight are important attributes.
The higher the size or molecular weight of a
substance, the most efficiently it is excluded.
Thus virus, bacteria, and pyrogen are removed by
reverse osmosis.
The overall system primarily depends on the
composition of feed water and the quality of the
final water desired.
In addition to RO unit, other type of systems may
include chlorinators, flocculating agents, filters,
water softeners, heat exchangers, active carbon
beds, decarbonators, deionizers etc.,
15. DISTILLATION:
The action of purifying a liquid by a process of
heating and cooling.
The process of removal of impurities from the
liquid by continuous heating above 100 degrees
and at atmospheric pressure cooling
simultaneously.
This aids in killing the living microorganisms.
Prior to distillation, water used as source for WFI
should be done with pretreatment
Perfect phase change would leave all the
impurities behind producing pure water vapor.
After this the vapor is condensed to liquid water.
16. .
It is maintained at pressure greater than the water
of lower purity.
The objective is to control the number of
organisms per unit volume of water used for final
rinses of equipment and containers.
After distillation it is filtered and stored in a
chemical resistant stainless steel tank at a cold
temperature around 5c or at an elevated
temperature between 65-85 c to inhibit the
microbial growth and pyrogen formation.
18. CONTAINERS:
There are different types of containers used for
packing parenteral solutions. They are:
1) Glass containers.
Type I
Type II
Type III
NP
Generally, glass containers are used in
packaging of vials and ampoules.
2) Plastic containers.
They are used in packaging of large volume
parenterals like saline bags.
19. CLOSURES:
The mainly used closures for packing the
containers in parenteral preparations are rubber
closures.
Rubber closures and rubber extractives have
been found to influence preservative loss from
solution and antimicrobial activity respectively.
Generally used rubbers are natural and neoprene
rubber.
Loss of preservatives like chlorobutanol, methyl
paraben, benzyl alcohol, etc was minimal in the
presence of butyl rubber.
20. TERMINAL STERILIZATION:
A process whereby a product is sterilized in its
final container or packaging, which permits the
measurement and evaluation of quantifiable
microbial lethality.
In principle, the SAL should be less than 10-6.
Terminal sterilization refers that the finished
product should withstand with steam sterilization
cycle for 15minutes.
This process helps to assure the sterility of the
finished goods.
21. BLOW FILL SEAL (BFS):
Blow fill seal technology is most widely used and
accepted by USFDA.
Polypropylene granules are heated at 200 c to
form tube shaped parison
Parison reaches the mould forming container by
the sterile compressed air.
Fill nozzle known as mandrel fills the liquid in the
container
Followed by sealing neck and filled container is
released from the mould.
22. .
It takes 10-15 secs of time to produce one
container.
This method is followed to achieve the
contamination rate below 0.1%.
23. .
Rommelag’s BFS bottle-pack -321 machine
forms 3000 bottles(1000ml) in 1 hr with 6 moulds.
24. PRODUCTION FACILITIES:
◦ Clean- up area.
◦ Preparation area
◦ Aseptic area
◦ Quarantine area
◦ Finishing and packaging area
26. COMPARISION:
PARAMETERS SVP LVP
Volume <= 100 ml 101-1000 ml
Route IV, IM, SC IV
Dosage unit Single or Multiple Multiple
Preservative Used Not used
Buffer Used Not used
Isotonicity Not essential Must
Pyrogenicity Not essential Must
Formulations Solution.
Emulsion,
Suspension.
Solution,
o/w emulsion.
Uses As therapeutic agent,
As diagnostic agent.
As nutrition,
Detoxification,
Aid during surgery.
