This document provides an overview of the formulation and development of parenteral products. It discusses the key components including containers, closures, processing, formulation, production facilities, and evaluation methods. The production area is divided into five sections - cleanup, preparation, aseptic, quarantine, and finishing/packaging areas. Parenteral formulations contain active drugs, vehicles, and adjuvants. Finished products undergo sterility, clarity, leakage, pyrogen, and assay testing to ensure quality control.

1. Formulation and development
of
parenterals
Presented by:
SAI DHATRI ARIGE
V. V. Institute of Pharmaceutical Sciences

2. Contents:
• Introduction
• Containers and closure
• processing
• Formulation and production
• Evaluation
• References
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3. Parenteral
Parenteral refers injectable route of administration.
It derived from Greek words Para (Outside) and
enteron (Intestine).
So it is a route of administration other than the oral
route. This route of administration bypasses the
alimentary canal
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4. Containers:
1. Glass:
• Highly Resistant Borosilicate Glass
• Treated Soda lime Glass
• Regular Soda Lime Glass
• N.P (Non-parenteral) Glass
Type 4 is not used for parenteral packaging, others
all are used for parenteral packaging.
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5. 2. Plastic:
Plastic containers are used but they face following problems
• Sorption
• Leaching
• Softening
3. Rubber:
To provide closure for multiple dose vials, IV fluid bottles, plugs for disposable
syringes and bulbs for ophthalmic pipettes, rubber is the material of choice.
Problems associated with rubber closures are
• Incompatibility
• Chemical instability
• Physical instability5 Pharmaceutics

6. Closure:
• Characteristics of Good Pharmaceutical rubbers
• Good ageing qualities
• Satisfactory hardness and elasticity
• Resistance to sterilization conditions
• Impermeable to moisture and air
• Examples:
• Butyl Rubbers
• Natural Rubbers
• Neoprene Rubbers
• Poly isoprene rubbers
• Silicone Rubbers
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7. SYSTEM
COMPONE
NT
Preparatio
n
Area
Storage
Area
Personnel
Policies
and
Procedures
Admixture
system
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8. PROCESSING OF
PARENTERALS
S. No. STEPS
1. Cleaning of containers, closures and equipments
2. Collection of materials
3. Preparation of parenteral products
4. Filtration
5. Filling the preparation in final containers
6. Sealing the containers
7. Sterilization
8. Evaluation of parenteral preparation
9. Labeling and packaging
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9. Formulation of parenteral products
• In the preparation of parenteral products, the following substances are added to make
a stable preparation:
 The active drug
 Vehicles
 Aqueous vehicle (e.g. water for injection, water for injection free from CO2
)
 Non-aqueous vehicle (e.g. Ethyl alcohol, propylene glycol, almond oil)
 Adjuvants
 Solubilizing agents (e.g. Tweens & polysorbates)
 Stabilizers & antioxidants (e.g. thiourea, ascorbic acid, tocopherol)
 Buffering agents (e.g. citric acid, sodium citrate)
 Antibacterial agents (e.g. benzyl alcohol, metacresol, phenol)
 Chelating agents (e.g. EDTA)
 Suspending, emulsifying & wetting agents (e.g. MC, CMC)
 Tonicity factor (e.g. sodium chloride, dextrose)9 Pharmaceutics

10. Production facilities of parenterals
• The production area where the parenteral preparation are
manufactured can be divided into five sections:
Clean-up area
Preparation area
an aseptic area
Quarantine area
Finishing & packaging area
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11. Clean-up area:
 It is not an aseptic area.
 All the parenteral products must be free from foreign particles &
microorganism.
 Clean-up area should be withstand moisture, dust & detergent.
 This area should be kept clean so that contaminants may not be carried out into
an aseptic area.
Preparation area:
 In this area the ingredients of the parenteral preparation are mixed &
preparation is made for filling operation.
 It is not essentially an aseptic area but strict precautions are required to prevent
any contamination from outside.
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12. An aseptic area:
 The parenteral preparations are filtered, filled into final container & sealed
should be in an an aseptic area.
 The entry of personnel into an an aseptic area should be limited & through
an air lock system.
 Ceiling, wall & floor of that area should be sealed & painted.
 The air in the an aseptic area should be free from fibers, dust and
microorganism.
 The High efficiency particulate air filters (HEPA) is used for air.
 UV lamps are fitted in order to maintain sterility.
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13. Quarantine area:
 After filling, sealing & sterilization the parenteral product are held up in
quarantine area.
 Randomly samples were kept foe evaluation.
 The batch or product pass the evaluation tests are transfer in to finishing or
packaging area.
Finishing & packaging area:
 Parenteral products are properly labelled and packed.
 Properly packing is essential to provide protection against physical
damage.
 The labelled container should be packed in cardboard or plastic container.
 Ampoules should be packed in partitioned boxes
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14. EVALUATION OF PARENTERAL
PREPARATIONS
• The finished parenteral products are
subjected to the following tests, in order to
maintain quality control:
A) Sterility Test
B) Clarity Test
C) Leakage Test
D) Pyrogen Test
E) Assay
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15. A) Sterility test
• It is a procedure carried out to detect and conform
absence of any viable form of microbes in or on
pharmacopeia preparation or product.
1) Method of sterility testing
i ) METHOD 1 Membrane filtration method
ii) METHOD 2 Direct inoculation method
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16. B)Clarity test
• Particulate matter is defined as unwanted mobile insoluble matter
other than gas bubble present in the product.
• If the particle size of foreign matter is larger than the size of R.B.C..
It can block the blood vessel.
• The permit limits of particulate matter as per I.P. are follows:
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17. C)Leakage test
• The sealed ampoules are subjected to small cracks which occur due
to rapid temperature changes or due to mechanical shocks.
Filled & sealed ampoules
Dipped in 1% Methylene blue solution
Under negative pressure in vacuum chamber
Vacuum released colored solution enter into the ampoule
Defective sealing
Vials & bottles are not suitable for this test because the sealing
material used is not rigid17 Pharmaceutics

18. D)Pyrogen test
 Pyrogen = “Pyro” (Greek = Fire) + “gen” (Greek =
beginning).
 The presence of pyrogens produces metabolic by products
which leads to increase in fever and further increase in
microbial growth leads to death
 Bacterial pyrogens are called “Endotoxins”. Gram negative
bacteria produce more potent endotoxins than gram + bacteria
and fungi.
 Endotoxins are heat stable lipopolysaccharides (LPS) present
in bacterial cell walls, not present in cell-free bacterial filtrates
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19. E)Assay
• Assay is performed according to method given In the
monograph of that parental preparation.
• Assay is done to check the quantity of medicament
present in the parenteral preparation.
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20. References
• Encyclopedia of pharmaceutical technology by James Swarbrick
pg.no.1266-1299
• Pharmaceutical product development by N.K.JAIN
• Chemical Incompatibility of Parenteral Drug Admixtures; T. J.
Mccarthy; S.A. Medical journal 2
• The theory & pratice of “Industrial Pharmacy” Leon Lachman ,Herbert
A. Liberman.special Indian Edition 2009 Pg. No.693-680.
• Modern Pharmaceutics Fourth Edition, Revised and Expanded, Edited
By G.S. Banker & C.T. Rhodes, Marcel Dekker pg387-389.
• The Science & practice of Pharmacy, By Remington, Vol-01, Edi.21st,
Lippincott Publication, pg-838-840.
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