Stability of a pharmaceutical formulation:-
Stability of a drug can be defined as its ability in a specific container to remain with in proscribed standards of physical , chemical ,therapeutic and toxicological specifications to ensure the identity strength and quality and purity of a formulation .
What is period of stability ( Shelf life of a formulation)
Shelf life of period of stability of a pharmaceutical preparation can be defined as the time from which it is manufactured , till it remains and chemically ,biologically , active and passes the tests laid downs as standards in a pharmacopoeia such as Assay and impurities and physicochemical changes and all organoleptic properties of a dosage form passes with in the proscribed limits of monograph in particular pharmacopoeia.
Reasons for stability studies:
1.Ensure safety of a dosage form and drug
2.Ensure maintenance of efficacy of dosage form and drug through out the self life
Degradation of pharmaceutical products:
Physical degradation :- Due to temperature shocks , light and moisture ,
Physical degradations example could be , phase separation in a cream , or fading of colour in a preparation , or forming hard sedimentation in a suspension, formation of precipitation, loss of volatile constituent , or moisture absorption, crystal growth , or polymorphic changes in crystal .
Examples could be polymerisation of monomers , oxidation , reduction , solvolysis reactions, photolysis , dehydration , racemisation, decarboxylation, pyrolysis, complexation , and breaking down a complex in final formulation, and chemical incompatibilities.
I will like to give you a example of a stability study for an Injection of ascorbic acid, as it gives good results in a laboratory if you wan to teach any stability study analysis.
Ascorbic acid injection containing following ingredients is studied for stability
1.Ascorbic acid 0.5 gm
2.Sodium metabisulfate 0.1 %
3.Di sodium EDTA 0.1%
4.Sodium bicarbonate Qs
5.Water for injection 2.0ml
6.Chlorocresol 2.0 %
Procedure for accelerated stability studies
Fill this solution after it is rendered sterile by using method of filtration sterilisation for injectable by passing through 0.02 micron cellulose acetate filter , other containers and closures presteriliesed and solution is aseptically filled in to ampules and sealed.
These ampoules are kept for following temperature
AT ROOM TEMP
AT 37 °C
AT 45 °C
AT 60 °C
and these are assayed after 7 , 14, 21 , 28 Days intervals
How Ascorbic acid get degraded in water
Ascorbic acid is a unsaturated lactone cyclic ester , it is easily oxidised in liquid form , and degradation is enhanced by light, the degradation reaction is a reversible reaction
Ascorbic acid <-----------> Dehydro ascorbic acid -----> Diketogluoconic acid ---->Oxalic acid
Diketogluoconic acid is brown in colour hence ascorbic acid in process of degradation is brown in colour.
This is a oxidation reaction , it is dependant on PH and it is catalysed by presence of metal ions like Cu++ Fe++
Degradation is enhanced in open container which is not protected from external air , and light
Degradation reactions are of following types
1.First order reaction :- Degradation depends on concentration of one substrate
2.Second order reaction:- Degradation is dependant on any of other molecule along with actual drug molecule .
3.Zero order reaction :- Degradation is purely dependant on catalyst or sunlight ,or atmosphere
One should study these factors in detail so that a final product can be formulated in a better way and its stability is enhanced , write such reaction mechanisms beyond caring out estimations and assay.
We can derive the actual stability period of any formulation by putting the data of assay results derived after specific time period , by putting it in to equation
T= (2.303/K ) X (log C0 -log Ct)
plot a graph of time against concentration observed for particular temperature
and find the slope of the graph this is your value of constant K , from this you can find out for how many days this product is going to be stable .
Basic information about pharmaceuticals and pharmacy related to pharmaceuticals over this blog
Quality management guide for pharmaceuticals
Quality Guide for pharmaceuticals
Quality assurance in pharmaceuticals
Pharmacy guide Sterile dosage form----------->