3. Stability testing
The purpose of stability testing is to provide evidence on how
the quality of an active pharmaceutical ingredient or
medicinal product varies with time under the influence of a
variety of environmental factors such as temperature,
humidity, and light, and to establish a re-test period for the
active pharmaceutical ingredient or a shelf life for the
medicinal product and recommended storage conditions.
4. Stability of drugs
The ability of the pharmaceutical dosage form to
maintain the physical, chemical, therapeutic and
microbial properties during the time of storage and
usage by the patients.
Stability include attributes of the active
pharmaceutical ingredient that are susceptible to
change during storage and are likely to influence
quality, safety, and/or efficacy.
5. Expiration date
The date placed on the container label of a drug
product designated the time prior to which a batch of
the product is expected to remain with in the
approved shelf life specification, if stored under
defined conditions, and after which it must not be
used
6. Shelf life
The time period during which a drug product is expected to
remain within the approved shelf life specification, provided
that it is stored under the conditions
The time period during which the drug maintain its
90%potency or loss not more than 10% potency
7. Climate zones
The design of the stability-testing programme should take into account
the intended market and the climatic conditions in the area in which the
medicinal products will be used.
Four climatic zones can be distinguished:
Zone 1:temperate
Zone 2:subtropical, with possible high humidity
Zone 3:hot/dry
Zone 4:hot/humid
The shelf life should be established with due regard to the climatic
zone(s) in which the products are to be marketed
8. Stress testing
Stress testing of the active pharmaceutical ingredient can help identify
the likely degradation products, which can in turn help establish the
degradation pathways and the intrinsic stability of the molecule.
Stress testing is likely to be carried out on single batch of the active
pharmaceutical ingredient. It should include the effect of temperature (in
10C increment) above that for accelerating testing , humidity (e.g., 75%
RH or greater) where appropriate oxidation and photolysis on the API.
The testing should evaluate the susceptibility of the API to hydrolysis
across a wide range of pH values when in solution or suspension.
Photo stability testing should be an integral part of stress testing
9. Storage conditions
API should be evaluated under storage conditions (with
appropriate tolerance) that test its thermal stability and, if
applicable, its sensitivity to moisture.
10. General case
Minimum time period
covered
Storage conditionsStudy
12 months25ºC ± 2ºC/60% RH ± 5%
RH
or
30°C ± 2°C/65% RH ± 5%
RH
Long term
6 months30ºC ± 2ºC/65% RH ±
5%RH
Intermediate
6 months40ºC ± 2ºC/75% RH ± 5%
RH
Accelerated
11. If long term studies are conducted at 25ºC ± 2ºC/60% RH ±
5% RH and “significant change” occurs at any time during 6
month testing at the accelerated storage condition, additional
testing at the intermediate storage condition should be
conducted and evaluated against significant change criteria.
Significant change: failure to meet specification, loss of 5 % potency
12. Storage in a refrigerator
Minimum time period
covered
Storage conditionsstudy
12 months5ºC ± 3ºCLong
6 months25ºC ± 2ºC/60% RH ± 5%
RH
Accelerated
14. Testing frequency
For long term studies, frequency of testing should be
sufficient to establish the stability profile of the
pharmaceutical product.
For products with a proposed shelf life of at least 12 months,
the frequency of testing at the long term storage condition
should normally be every 3 months over the first year, every
6 months over the second year, and annually thereafter
through the proposed shelf life.
15. FrequencyStudy
0,3,6 and one additional time pointAccelerated time points
0,3,6,9,12,18,24,36 monthsLong time points
16. Parameters checked during testing
Dissolution/ release of pharmaceutical product
Assay /percentage purity of pharmaceutical product
Physical characters of pharmaceutical product
pH (in case of liquid)
17. Accelerated test for stability
When determining the chemical stability of a product, assay
employed should be sufficiently specific to distinguish
between the drug and its decomposition product.
Acceleration of chemical decomposition is achieved by
Raising the temperature of the preparation.
The order of reaction for the decomposition process is
determined by plotting the appropriate function of
concentration against time and obtaining a linear relationship
18. The reaction velocity constant, k, for the de composition at
each of the elevated temperature can be calculated from the
slope of the line
The Arrhenius relationship is then employed to determine
the reaction velocity constant ,k, at room temperature.
This is obtained from the linear plot of the log of determined
reaction velocity constant, k, against the reciprocal of
absolute temperature, which is extrapolated to room
temperature 25 C
20. Estimation of shelf life
The value of k at 25 C substituted in the Arrhenius equation
and an estimate obtained of the time during which the
product will maintained the required quality or potency (shelf
life)
Limitations: the predicted shelf life of a preparation will only
be valid if the accelerated test is carried out on the final
packaged product.
Applied only those form of decomposition which increase
with rise in temperature.
21. References
Q1A(R2) Stability Testing of New Drug Substances and Products
Alfred martin, physical pharmacy ,edition (4)
Bentley's text book of pharmaceutics edition (8)
