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Advantages Disadvantages
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Sterility (must)
Pyrogen (must) Most Common: 1. Subcutaneous (SC; SQ ;Sub Q)
Free from particulate matter (must) 2. Intramuscular (IM)
Clarity (must) 3. Intravenous (IV)
Stability (must)
Isotonicity (should) Others: 4. Intra-arterial (IA)
Solvents or vehicles used must meet special purity and other 5. Intrathecal
standards. 6. Intraarticular
Restrictions on buffers, stabilizers, antimicrobial preservative. Do 7. Intrapleural
not use coloring agents. 8. Intracardial
Must be prepared under aseptic conditions. 9. Intradermal (Diagnostic)
Specific and high quality packaging.
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Intrathecal: Intraarticular:
Also called intra-spinal Given directly into the joints
Directly given into the spinal cord 2 to 20 ml
1 to 4 ml 5 inch 22 gauge
24 to 28 gauge Must be isotonic
Must be isotonic
Given:
Given: Morphine
LA (Local anaesthetic) LA
Analgesics Steroids
Neuroleptics NSAIDs
Antibiotics
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Intrapleural: Intracardial:
Given directly into the pleural cavity or lung Directly given into the heart
Used for fluid withdrawal 0.2 to 1 ml
2 to 30 ml
2 to 5 inch, 16 to 22 gauge needle 5 inch , 22 gauge needle
Given: Given:
LA
Narcotics Cadiotonics
Chemotherapeutic agents Calcium salts as a calcium channel blockers
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Given:
Diagnostic agents
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iii. Antioxidants:
Used to protect product from oxidation.
Acts as reducing agent or prevents oxidation.
ii. Preservatives:
Examples
Multidose containers must have preservatives unless A) Reducing agent:
Ascorbic acid -- 0.02 0.1 %
prohibited by monograph. Sodium bisulphite-- 0.1 0.15 %
Large volume parenteral must not contain preservative Sodium metabisulphite-- 0.1 0.15 %
Thiourea - 0.005 %
becoz it may be dangerous to human body if it contain B) Blocking agents:
in high doses. Ascorbic acid esters- 0.01 0.015%
BHT- 0.005 0.02 %
C) Synergistic:
Ascorbic acid , Citric acid , Tartaric acid
D) Chelating agent:
EDTA- 0.01- 0.075 %
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iv. Buffers:
Added to maintain pH, v. Chelating agents:
Change in pH may causes degradation of the products Used to form the complex with the metallic ions present in the
Acetates, citrates, phosphates are generally used. formulation so that the ions will not interfere during mfg. of
Factors affecting selection of buffers: formulation.
Effective range, They form a complex which gets dissolved in the solvents.
Concentration
Chemical effect on the total product
Examples:
EXAMPLES: Disodium edetate 0.00368 - .05 %
Acetic acid ,adipic acid, benzoic acid, citric acid, lactic acid Disodium calcium edetate - 0.04 %
Used in the conc. of 0.1 to 5.0 % Tetrasodium edetate 0.01 %
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Clean area:
Non aseptic area.
S COMPOUNDING ASEPTIC QUARANTINE
Free from dust ,fibres & micro-organisms.
T AREA AREA AREA
Constructed in such a way that should withstand moisture,
O
C STORAGE steam & detergent.
K
AND Ceiling & walls are coated with material to prevent.
R TRANSPORT accumulation of dust & micro-organisms.
O
O PACKING Exhaust fans are fitted to remove heat & humidity.
M CLEAN UP
AREA
STERILIZATION AND The area should be kept clean so that to avoid
LABELLING
contamination to aseptic area.
The containers & closures are washed & dried in this area.
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Aseptic area:
Preparation area: Filtration & filling into final containers & sealing is done
The entry of outside person is strictly prohibited
The ingredients are mixed & prepared for filling
To maintain sterility, special trained persons are only
Not essential that the area is aseptic allowed to enter & work
Strict precaution is taken to prevent contamination from Person who worked should wear sterile cloths
outside Should be subjected for physical examination to ensure
the fitness
Cabinets & counters: SS
Minimum movement should be there in this area
Ceiling & walls : sealed & painted Ceiling & walls & floors : sealed & painted or treated with
aseptic solution and there should not be any toxic effect
of this treatment
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threshold bench.
White area gloves
Aseptic area where the preparation takes place.
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Batch type- Vials are dipped in the netted blanket where washing and sterilization is done.
This process is carried out in aseptic area under laminar air flow
Continuous type-
Utilize rotary washing machine, one after another with cleaning
agents.
Cleaning agents-
Hot detergent water under high pressure
Tap water
Deionized water
Distilled water
WFI
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Requirements
Non aqueous oil based vehicle. 1) Medicament
Solvent which are miscible in water are usually used in 2) Excipients
combination with water as the vehicle. Buffer
Solution must not irritating, toxic and sensitive. Antioxidants
Dont have adverse effect. Preservatives
Ex- Solubilizing agent
Dioxalane Suspending agent
Ethyl acetate. 3) Deionized water
4) Containers
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Structure of endotoxins
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These are the reasons why pyrogens are difficult to destroy once
produced in a product
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Removal
Distillation-effective for water as pyrogens are non volatile.
Ultrafiltration-combination of ultra filter (0.1 ) and sterilization
filter (0.2 ).
Ion exchanger-using resin.
Gamma irradiation.
Ringing container/equipment-with pyrogen free water.
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