Guide for pharmaceuticals manufacturing and pharmacy Guide for pharmaceuticals Guide for pharmacy
Injectable preparations are sterile dosage form containing one or more medicament’s intended for administration in to body tissue or directly in to body fluid .
Injectable preparations should be manufactured by adapting and designing manufacturing procedure which will ensure that the product manufactured is sterile and pyrogen free.
I have given in details about what is sterility and what are the pyrogens how injectable dosage forms are tested for freedom from pyrogen , i have given every thing over this blog.
Injection constitutes following ingredients.
1.Vehicle
3.Medicament or active ingredient
2.Additives
3.Preservatives
4.Containers
5.Closures.
Besides this injection , Intramuscular and large volume parantrals are required to be isotonic with blood.
That means the pressure inside a blood cell and parantral preparation is exactly equal so that the blood cells do not swell and burst or shrink in size , that means how important is this factor in intravenous preparations .
1.Vehicle in injection dosage form
Injections which are liquid or suspensions require a vehicle in which medicament or a drug is incorporated .In case of water soluble drug molecules most of time water for injection is mainly used as vehicle .When ever the use of water for injection is directed to be used for a particular injection a freshly prepared water for injection must be used, sterilisation step at this point can be omitted provided the final product is immediately sterilised .Where ever water for injection is required to be free from any dissolved gasses and carbon dioxide ,water for injection freshly prepared is boiled for at least 10 mins with no exposure to air and environment , this can be achieved by heating in an autoclave.
Vehicle for aqueous injection should pass the test for pyrogen .
Fixed oils and esters as ethyl olate may be used as vehicle for oily or non aquious injections.Fixed oils are of vegetable origin are colour less or nearly colour less, should have no odour or taste and free from rancidity, any other suitable vehicle may be used provided it is proved that it is safe in the volume injected in human being ,and should not interfere or alter pharmaceutical efficacy of drug molecule being incorporated.
Added substances (Additives in injection):
A suitable substance may be added in to formula of a injection to increase stability or other useful effect or property ,in a concentration in which that used substance is harmless and do not alter or affect adversely the effect of medicament of injectable preparation , should not interfere in the tests or process of estimation by chemical and instrumental analysis to assay active ingredient of injectable dosage form.
Colouring agent should not be added for purpose of colouring finished formulation intended for parantral administration.
Isotonic solutions for injection:
Aqueous injectable preparations which are administered Intramuscularly
or in case of large volume intravenous route are required to be made isotonic with blood , this can be achieved by addition of sodium chloride or other suitable agent.
Buffering agents :- Should not be used in injectable preparation where the injection is intended for intraocular use or intrathecal , or injection which comes directly with ceribrospinal fluid.
Preservatives used in injections:
A suitable substance or combination of one or more substance can be used to prevent the growth of microorganism must be added to preparation intended for parantral use which are packed in multi dosage containers , though the sterilisation .In case if the drug molecule is thermolabile a suitable bacteriostatic agent should be used in such a minimum concentration that it will prevent growth or kill microorganisms in the preparation for injection, a sterilisation process should be applied even though such substance is added , in some injections air in the container of injectable is required to be replaced by chemically inert gas such as nitrogen.
Sterilisation: A suitable sterilisation method suitable as given in USP or BP should be adapted.
Refer my earlier post over this blog i have given in detail about sterilisation methods over this blog as well as here http://www.microbiology1.blogspot.com/
Containers used for Injections:
Containers used for injectable preparation are made from material which is sufficiently transparent to permit visual inspection of the content of injectable preparation and which do not interact with drug molecule incorporated chemically with injection in any manner ,should not alter strength quantity and purity of injection which will make the preparation fall out of standards of pharmacopoeia at ordinary conditions while storage and transportation.
Containers for injectable preparations are closed by fusion or fitted with a closure in such way that it prevent the microbial or particulate contamination and protect the loss of content .
Single dose containers are used for administration of whole content at once , intrathecal , intramuscular , or iv bolus .
Multi dosage containers permit withdrawal of content in successive portion by syringe ,without destruction of closure and without changing the strength and quality or purity and keeping the preparation sterile through out the complete usage, it may be about 10 dosage , there is a specific guideline for usage period from 1st dosage to last dosage.
Closure for injection :Closures tend to absorb preservative from injection solution by processes of absorption and adsorption , hence they are placed in a sloution of antimicrobial agent which is being used in injectable preparation , taking concentration of antimicrobial preservative in water for injection equal to twice that of used in actual formulation keeping them for sufficient time so that it get saturated with antimicrobial preservative and further will not absorb any antimicrobial preservative from actual injectable liquid where it will be used.
Same method can be adapted where there are chances of loosing concentration of other ingredients which are added in ingredients , like wise they can be too saturated in to rubber closure to avoid absorption from actual injectable preparation.
i have provided detailed information about closure for injection in my earlier post.
Visual Inspection of injectable dosage form:
C GMP requires that each and every container of a injectable dosage form should be visually inspected for any particulate or foreign matter and should be discarded .
Appearance :
Injection which are emulsions should not show any evidence of separation and should show a uniform appearance after shaking , injections which are suspensions should be redispersible easily after sedimentation , and should remain sufficiently dispersed to allow withdrawal of a correct dose , if injection is a powder for reconstitution before use , it should be reconstituted with the proscribed vehicle mostly water for injection and should be clear and practically particle free, should not have any undissolved solid.
Particulate matter:
injectable preparations which are solutions , when examined under sufficient illumination and magnification, for visibility should be practically free from particulate matter.
Sterility test for injection:
Injectable dosage form should comply the test for sterility .
i have given over this blog in my earlier post detailed information about sterility test, test for pyrogen etc , what you have to do is search in blog archive over this blog , so search there each and every page on t his blog is very informative for a pharmacists and for pharmaceuticals manufacturing pharmacist.
Test for pyrogen:Injectable preparation should be practically free from pyrogens
Besides this injectable preparations should meet the required standards of
Extractable volume
Content of active ingredient , that is Assay of active ingredients.
Injectable preparations should comply with respective pharmacopoeia standards.
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Basic information about pharmaceuticals and pharmacy related to
Quality management guide for pharmaceuticals
Quality Guide for pharmaceuticals
Quality assurance in pharmaceuticals
Pharmaceuticals guide
Pharmacy guide
Sterile dosage form