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, therapeutic and toxicological specification.
Need for stability testing:
1. Provide evidence as to how the quality of the drug
product varies with time.
2. Establish shelf life for the drug product.
3. Determine recommended storage conditions.
4. Determine container closure system suitability.
5. Safety point of view of patient.
6. Prevention of expenses.
7. Essential quality attribute.
8. To save time and money.
Types of Stability
Type Condition to be
1.Chemical : Chemical integrity &
4.Therapeutic: Drug action remains
5.Toxicological: No increase in toxicity
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
ARRHENIUS EQUATION :
Arrhenius equation gives "the dependence of the rate constant k
of chemical reaction on the temperature T and activation energy
Ea", as shown below:
Where k=specific rate constant
Ea= activation energy
R=ideal gas constant
Take log on both sides,
ln k = ln A –Ea/RT ln e (2)
Converting eq. 2 to log 10
log k = log A – Ea/2.303RT
TYPES OF STABILITY TESTS:
Long term stability tests
Accelerated stability tests
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.
Tests at elevated temperature:
Drug liquid preparation stored at 50, 60, 70,85,100 and
Also study performed at R.T. and or refrigerator temp.
First year- 3 month interval
Second year- 6 month interval
Four climatic zones:
Temperate zone 21˚c/45%RH
Mediterranean zone 25˚c/60%RH
Tropical zone 30˚c/70%RH
Desert zone 30˚c/35%RH
Tests at high intensity of light:
Drug substances darken on exposing to light, can be controlled by
using amber glass or opaque container.
By exposing drug substance to 100& 121(fc)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 spectroscopy for examination.
e.g. cycloprofen becomes very yellow after five days exposing to light.
Tests at high partial pressure of oxygen:
Here, high oxygen tension plays important role to
investigate stability Usually ,40% of oxygen atmosphere
allows for rapid evaluation.
Results were correlated with inert & without inert
Tests at high relative humidity:
Presence of moisture may cause hydrolysis and oxidation.
These reactions may accelerated by exposing the drug to
different relative humidities.
Control humidity by Lab desiccators
Closed dessicator are placed in an oven to provide constant
LIMITATIONS OF ACCELERATED STABILITY TESTING
Valid only when the break down depends on temperature.
The energy of activation obtained in the study should be
between 10 to 30 kcal/mole.
It is not useful when degradation is due to:
• Microbial contamination
• Excessive agitation
When the product looses its physical integrity at higher
When the order changes at elevated temperatures.
ICH GUIDELINES ON STRESS TESTING:
Standard Title and reference
ICH Q1A(R2) Stability Testing of New Drug Substances and
Products (the parent guideline)
ICH Q1B Photostability Testing of New Drug
Substances and Products
ICH Q C Stability testing of new dosage forms
ICH D Bracketing and matrixing designs
ICH Q E Evaluation of stability data
ICH Q F Stability data package for registration
applications in climatic zone I and IV
Martin’s Physical Pharmacy and Pharmaceutical Sciences.
Patrick J.Sinko ,
Theory and practice of Industrial Pharmacy – Lachman
International Stability Testing Drug stability- Cartensen
Textbook of Physical Pharmaceutics C V S Subrahmanyam