Stability Testing

PRESENTED BY

SANA IJAZ

10-M-PCEU-2014

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.

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.

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

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

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

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

Storage conditions

API should be evaluated under storage conditions (with appropriate tolerance) that test its thermal stability and, if applicable, its sensitivity to moisture.

General case

Minimum time period covered

Storage conditions Study

12 months 25ºC ± 2ºC/60% RH ± 5% RHor30°C ± 2°C/65% RH ± 5% RH

Long term

6 months 30ºC ± 2ºC/65% RH ± 5%RH

Intermediate

6 months 40ºC ± 2ºC/75% RH ± 5% RH

Accelerated

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

Storage in a refrigerator

Minimum time period covered

Storage conditions study

12 months 5ºC ± 3ºC Long

6 months 25ºC ± 2ºC/60% RH ± 5% RH

Accelerated

Storage in freezer

Minimum time period covered

Storage Study

12 months -20ºC ± 5ºC Long

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.

Frequency Study

0,3,6 and one additional time point Accelerated time points

0,3,6,9,12,18,24,36 months Long time points

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)

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

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

Arrhenius equation and plot

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.

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)