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PARENTRALS
CONTENTS
Introduction Routes of administration Advantages Disadvantages Preliminary stages Formulation Manufacture Filling Packaging Sealing Sterilization Quality control Conclusion References
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INTRODUCTION
DEFINITION According to USP :
A BRIEF ABOUT PARENTERALS : para: outside enteron: intestine Any drug or fluid whose delivery does not utilize the alimentary canal for entry into body tissues.
Parenteral products are injected through the skin or mucous membranes into the internal body compartments. These are the preparations which are given other than oral routes.
ROUTES OF ADMINISTRATION
Three primary routes of parenteral administration are commonly employed : Subcutaneous Intramuscular Intravenous Other routes : Intra arterial Intra athecal Intra articular Intra cardial Intra dermal Intra pleural Intra spinal Intra vascular
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Parentrals are classified into two types. They are 1. Small Volume Parenterals (upto 100ml) Primary uses of SVP
Diagnostic agents
Allergenic extracts
ADVANTAGES
Quick onset of action Suitable for the drugs which are not administered by oral route Useful for unconscious or vomiting patients. Useful for patients who cannot take drugs orally Useful for emergency situations Duration of action can be prolonged by modifying formulation.
Can be done in hospitals, ambulatory infusion centers, and home health care
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DISADVANTAGES
Pain on injection. Difficult to reverse an administered drugs effects. Sensitivity or allergic reaction at the site of injection. Requires strict control of sterility & non pyrogenicity than other formulation. Only trained person is required Require specialized equipment, devices, and techniques to prepare and administer drugs. More expensive and costly to produce.
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PRELIMINARY STAGES
It includes : - Material management - Equipment and facility management - Personnel management - Documentation control
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FORMULATION
Aqueous vehicle : Water For Injection(WFI) USP :
Highly purified water used as a vehicle for injectable preparations which will be subsequently sterilized.
USP requirement include not more than 10 parts per million of total solids. pH of 5.0 to 7.0 WFI may prepared by either distillation or reverse osmosis. Stored for less than 24hr at RT or for longer times at specific temperatures. It may not contain any added substances. Stored in chemically resistant tank.
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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.
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Water-miscible vehicles :
primarily to effect solubility of drugs and/or reduce hydrolysis
Non-aqueous vehicles :
Fixed oils (vegetable origin, liquid, and rancid resistance, unsaturated, free fatty acid content)
Peanut oil Corn oil Cotton seed oil (depo-testosterone) Sesame oil Soybean oil (source of fat in intralipid) Ethyl oleate Isopropyl myristate
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OTHER ADDITIVES
Antibacterial Agents
Required to prevent microorganism growth Limited concentration of agents - Phenylmercuric nitrate and Thiomersol 0.01% - Benzethonium chloride and benzalkonium chloride 0.01% - Phenol or cresol 0.5% - Chlorobutanol 0.5%
Buffers
Added to maintain pH Results in stability Effective range, concentration, chemical effect
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Tonicity Agents
Reduce pain of injection Can include buffers
Chelating agents
ethylenediamine tetraacetic acid
- Sodium chloride
- Potassium chloride - Dextrose - mannitol sorbitol CO2 (sodium bicarbonate injection)
Inert Gases
N2 (gentamycin sulfate injection)
Surfactants
polyoxyethylene sorbitan monooleate sorbitan monooleate
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MANUFACTURING
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Processing Equipment
Container Components
Cleaning
Sterilization
Cleaning
Sterilization
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FILLING
1. Filling of liquids
A. Small volume parentrals Syringe based system Retraction device By gravity By pressure By vaccum
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2. Filling of solids
Scoop method Machine (Auger) method Problems Stratification Electrostatic charges Air pockets Clumping
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types of package
vial, ampoules, plastic containers, bottles syringe cartridges, plastic mini bags
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PACKAGING
Glass containers :
Type Description
Highly resistant I Borosilicate Treated Soda Lime glass Soda lime glass Powdered Glass
Type of Test
General Use
Buffered and unbuffered aqueous solutions All other uses Buffered aqueous solutions pH<7.0, Dry powders, Oleaginous solutions
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Water Attack
III
Powdered Glass
NP
Powdered Glass
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Plastic containers :
Thermoplastic
Polyethylene (Polyethene)High Density Polyethene Polyvinyl chloride (PVC) Poly methyl methacrylate Polystyrene Polypropylene Polyamides Polycarbonates
Closures :
Pharmaceutical rubbers
Butyl Rubbers Natural Rubbers
Thermosetting
Phenol Formaldehyde Urea Formaldehyde Melamine Formaldehyde
Neoprene Rubbers
Polyisoprene rubbers Silicone Rubbers
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PREFILLED SYRINGES :
Administration is more convenient for healthcare professionals and end
users.
Reduction of medication errors, better dose accuracy. Better use of controlled drugs such as narcotics. easy storage and disposal.
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SEALING
Sealing Ampoules
Ampoules are unique in that the primary and secondary seal are the same. Ampoules are sealed by melting a portion of glass in a flame. Pull seal Slow, Reliable, powder or other types with wide opening Roll or Tip seal
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STERILIZATION
Dry heat sterilization Steam sterilization Sterilization by filtration Gas sterilization Sterilization by ionizing radiation
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QUALITY CONTROL
Sterility testing
1. STERILITY TESTING
A . Membrane filtration
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2. PYROGEN TEST
A. Invivo test (Rabbit test)
Pyrogenic - means producing fever
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If above test not passes perform the test again If above test not passes, the sample is said to be pyrogenic and the test fails
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The name of the test is also Limulus amebocyte lysate (LAL) test
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Mechanism of LAL
The test is based on the primitive blood-clotting mechanism of the horse shoecrab enzymes located with the crab's amebocyte blood cells + endotoxins (pyrogens)
incubated at 37c
initiation of an enzymatic coagulation
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3. CLARITY TEST
Unwanted mobile insoluble matter other than gas bubbles present in the given product.
It may be dangerous when the particle size is larger than R.B.C. & may block the blood vessel.
It can be done by the following methods.
A. Visual method B. Light scattering & Light absorption C. Light blockage method D. Coulter current method
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4. Leakage Test
A. Dye test (Ampoules)
Immersing the ampoules in a dye solution 1% metylene blue solution The vacuum on the tank is then released as rapidly as possible to put maximum stress on weak seals. Defective ampoules will contain blue solution.
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CONCLUSION
A wide variety of devices and new methods of drug delivery employed. Each has its advantage and disadvantages, which have to be carefully considered by the therapist. Parenteral dosage forms differ from all other drug dosage forms because they are injected directly into body tissues through primary protective systems of human body the skin and mucous membranes. They must be free of contaminating microorganism, harmful substances, free of pyrogenic contamination, free of particulate matter. In coming future we can expect much more advance technology in utilizing parenteral products for safety desirable effects in human being.
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REFERENCES
Theory and practice of Industrial pharmacy. Lieberman, Herbert A. Vol.1.Lachman, Third edition
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