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Introduction Activation energy Arrhenius equation Accelerated stability testing Limitations of accelerated stability testing ICH guidelines References
Stability:
INTRODUCTION
Stability of pharmaceutical product may be defined as the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, therapeutic and toxicological specification.
ACTIVATION ENERGY:
It is defined as the energy that must be overcome in order for a chemical reaction to occur. Activation energy may also be defined as the minimum energy required to start a chemical reaction. The activation energy of a reaction is usually denoted by Ea, and given in units of kilojoules per mole.
ARRHENIUS EQUATION : Arrhenius equation gives "the dependence of the rate constant k of chemical reaction on the temperature T (in absolute temperature, such as Kelvin or degrees Rankine) and activation energy Ea", as shown below:
(1)
Where k=specific rate constant A=frequency factor Ea= activation energy R=ideal gas constant T=absolute temperature Take log on both sides, ln k = ln A Ea/RT ln e Converting eq. 2 to log 10 log k = log A Ea/2.303RT
(2)
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Estimation of k: 1.Reaction is conducted at several temp. 2.Conc. is determined at different time period. 3.Order of reaction is identified. 4.From slope of line k is calculated.
Fig. Estimation
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Time
Accelerated stability studies: Studies designed to increase the rate of chemical degradation or physical change of an active substance or drug product by using exaggerated storage conditions as part of the formal, definitive storage programme.
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Drug substances fade or darken on exposing to light, can be controlled by using amber glass or opaque container. By exposing drug substance to 400 & 900 (FC)of illumination for 4 & 2 weeks to light and another sample examined protected from light . Results found on appearance and chemical loss may be recorded. Comparing color or using diffused reflectance spectroscopy for examination. e.g. cycloprofen becomes very yellow after five days under 900 foot candles of light.
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Sensitivity of the drugs to atmospheric oxygen must be evaluated from which it should be packed in inert atmospheric condition with antioxidants is decided .
Here, high oxygen tension plays important role to investigate stability Usually ,40% of oxygen
Control humidity by Lab desiccators Closed dessicator are placed in an oven to provide constant temperature.
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When the product looses its physical integrity at higher temperatures. When the order changes at elevated temperatures.
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STABILITY PROTOCOL:
Containers and closures Container orientation Sampling interval Type, size and number of batches Plan of sampling Storage conditions Test methodology Acceptance criteria
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ICH Q1B
ICH Q C ICH D ICH Q E ICH Q F
REFERENCES
Lachman
THANK YOU
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