Page 75 - Quality control of pharmaceuticals (07-PA 704)

Stability information on both drug substance and drug products serves to assign the
shelf-life, determine appropriate storage conditions, and assure that the quality of
the product is unchanged from the time of manufacture to the time of administration
to the patient.
Forced Degradation Studies: (Stress testing)
Forced degradation studies involve the exposure of representative samples of drug
substance or drug product to the relevant stress conditions of light, heat, humidity,
acid/base hydrolysis and oxidation the results of forced degradation studies can
facilitate SIM development, drug formation design, selection of storage conditions,
and packaging.
Conditions for stress testing:
Specific parameters for stress testing of drug substances and drug product
describing the different stress conditions and range of exposure times must be
specified. The desired target extent of degradation is approximately 5-20%. This is
achieved by varying the stress conditions, for example, exposure time, temperature,
or concentration of stressing agent (acid, base, oxidizer, etc.)
Overstressing may destroy the compound or may lead to further degradation of the
relevant primary degradation. Under-stressing may fail to generate important
degradation products.
The concentration of drug in the stressed sample solution may affect the target level
of degradation. Lowering the drug concentration help to increase degradation.

1. Acid-base stress testing:

The function groups likely to undergo acid-base hydrolysis include: amides, esters,
imides, carbamates, alcohols, arylamines.
The stability of the drug substance should be at least 1mg/ml of 1N acid or base. If
the compound is insoluble in acids or bases, a co-solvent is required (alcohol should