processing and manufacturing of Small Volume Parenterals

1. processing and manufacturing of Small
Volume Parenterals
Prepared by Abhinay Ashok Jha from final year roll number 37 Guided
by Mr. shakeeb akhtar (associate professor)
continues assessment2018-2019
Khatoon Minority Women’s Social Welfare & Educational
Society’s
Royal College of Pharmaceutical Education & Research
Sayne Khurd, Malegaon. (NASHIK)
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2. INDEX
Sr. No. CONTENTS Slide no.
1 Introduction 3
2 Definition & Steps in processing 4
3 Formulation of svps 5
4 FORMULATION OF Suspension 12
5 Problem encounterd in suspension formulation are 15
6 Manufacturing 16
7 References 22
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3. Introduction
Small Volume Parenterals :
● All the sterile products packaged in vials, ampoules, cartridges, syringes, bottles or any
other container that is 100ml or less fall under the class of SVP.
● Ophthalmic products packaged in squeezable plastic containers, although topically
applied to the eye rather than administered by injection, also fall under the classification
of Small Volume Injections (SVI) as long as the container size is 100ml or less.
● SVP aqueous solutions can be administered by intravenous route because of local
irritation. Small volume parenteral products can be formulated and packaged in several
ways and include a wide variety of products like
● Pharmaceutical products. Biological products. Diagnostic agents. Allergenic extracts.
Radiopharmaceutical products. Dental products. Genetically engineered or
biotechnology products. Liposome and lipid products.
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4. DEFINITION
According to USP : “ an injection that is packaged in containers
labeled as containing 100 ml or less”
Steps in processing
● Selection of vehicle
● Antimicrobials Agents
● Buffers
● Surfactant
● Tonicity adjusters
● Suspending agent
● Emulsifiers
● Chelating agents
● Compexing agent
● Protein stabilisers
● Antioxidants
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5. Formulation of svps
1.vehicle
1. Aqueous vehicle :
○ 1.Water For Injection(WFI) USP Highly purified
water used as a vehicle for injectable
preparations which will be subsequently sterilized.
A. USP requirement include not more than 10 parts
per million of total solids.
B. pH of 5.0 to 7.0 WFI may prepared by either
distillation or reverse osmosis.
C. Stored for less than 24hr at RT or for longer
times at specific temperatures. Should be meet
USP pyrogen test It may not contain any added
substances.
D. Stored in chemically resistant tank.
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6. 2.Bacteriostatic Water for Injection
(BWFI) : This type of water used for
making parenteral solutions prepared
under aseptic conditions and not
terminally sterilized. Need to meet USP
sterility test. It can contain an added
bacteriostatic agent when in containers of
30ml or less
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7. 3.Sterile Water for Injection USP SWFI
containing one or more suitable bacteriostatic
agents. Multiple-dose containers not exceeding
30 ml. They are permitted to contain higher
levels of than WFI because of the possible
leaching of glass container. Sterile Water for
Irrigation. Wash wounds, surgical incisions, or
body tissue.
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8. 4.Water-miscible vehicles :
primarily to effect solubility of drugs and/or
reduce hydrolysis.
5.Non-aqueous vehicles :
Fixed oils (vegetable origin, liquid, and rancid
resistance, unsaturated, free fatty acid
content) – Peanut oil – Corn oil – Cotton seed
oil (depot testosterone) – Sesame oil –
Soybean oil (source of fat in intralipid) – Ethyl
oleate – Isopropyl myristate
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9. 2. Additives
1.Antimicrobials Agents;
Required to prevent microorganism growth
Limited concentration of agents -
Phenylmercuric nitrate and Thiomersol 0.01% Benzethonium chloride
and benzalkonium
chloride, Phenol or cresol 0.5%-Chlorobutanol 0.5%
2.Buffers;
Added to maintain pH Results in stability
Effective range, concentration, chemical effect e.g Citrate and Acetate
buffer, and Phosphate buffer
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10. 3.Tonicity adjusters
A) Electrolytes:Nacl
B) Non elecrolytes: Glucose ,Mannitol ,Glycerine
C) Ex. Of isotonic: Dextrose injection 5%&Nacl
injection 0.9%
D)Not important in IM& SC
E) Important in ID,intraspinal
F) Toncity can be measurement by:
osmometer,Fragility point
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11. 4. Surfactant: Polysorbate ethers
5. Suspending agent: Methyl cellulose,CMC,PVP
6. Emulsifiers:Lecithin
7.Chelating agents : Disodium EDTA
8. Compexing agent : 2-OH propyl b-cyclodextrane
9. Protein stabilisers: Amino acids,pvp
10. Antioxidants: Ascorbic acid,Cysteine
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12. FORMULATION OF Suspension
1) Parenteral suspension is a dispersed,
multiphased,heterogeneous system of insoluble
solid particles intended principally for
intramuscular and subcutaneous injection.
Because a delicate balance of variables is
required in order to formulate a suitable
product, a suspension is one of the most
difficult parenteral forms to prepare.
Such a product must not cake during shipping
and storage and should be easy to suspend
and inject through an 18 to 21 gause needle
throughout its shelf life.
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13. 2) To achieve these goals it is necessary to
control the crystallization, particle size
reduction, and sterilization of the drug
substance.
3) Suspension give prolong drug relese.particle
size of drug shoud be small and uniform.
4) Suspension require following additives wetting
agent , suspending agent , buffering agent,
preservative, antioxidant , ionicity agents
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14. Two basic method are used to prepare
parenteral suspension;
1 .sterile vehicle and powder are
combined aseptically.
2.sterile solutions combined and crystal
formed in situ.
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15. Problem encounterd in suspension
formulation are
a) Settling .
b) Polymorphic transformation.
C)Crystal growth
.
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16. Manufacturing
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17. 17

18. 18

19. 19

20. 20

21. References
1. Pharmaceutical Dosage Forms. Lieberman,
Herbert A. Vol. 1.
2. Parenteral Medications. Pharmaceutical Dosage
Forms. Avis, Kenneth E. Vol. 2
3. Parenteral Medications Pharmaceutical Dosage
Forms. Avis, Kenneth E Vol. 3
4. Parenteral Medications Parenteral Quality
Control. Michael J. Akers and Daniel S. Larrimore
(Marcel Dekker, second edition.1993).
5. Modern Pharmaceutics. Gilbert S. Banker,
Christopher T. Rhodes. Fourth Edition.
Vwww.google.com www.pharmaceuticalonline.com
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22. Thank you
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