Forced decomposition/degradation Studies

At times the solubility of a drug in water is insufficient at room temperature to allow a meaningful kinetic study, in which case it can, at times, be carried out at elevated temperature [58]. If done at several different temperatures, it may be possible to estimate the stability at room temperature by extrapolation. Frequently, a broad screen of stability is performed on the initial small sample used for initial performulation this is frequently referred to as forced decomposition studies [59], in which the drug is exposed to acid degradation, base degradation, aqueous degradation, drug powder... 

Even if the same drug substance HPLC method is used for the drug product, forced decomposition studies must be performed again for the drug product to confirm the resolution of potential degradation products from the API. In addition, forced decomposition studies must also be performed for different dosage forms (capsule, tablet, suspension, injectable, etc.) of the same drug substance. 

The guidance on forced degradation is available, as stated above however, the details of the investigations are left up to the pharmaceutical researcher. Forced decomposition testing within the pharmaceutical industry varies tremendously this was demonstrated by Baertschi [22], who surveyed 20 pharmaceutical companies on the practices of forced decomposition studies. 

The choice of stress conditions should be consistent with product decomposition under normal manufacturing, storage, and use conditions. Recommended stress factors include high and low pH, elevated temperature, photolysis, and oxidation. The extent of the stress applied in forced degradation studies should ensure formation of the desired amount (usually 10-20%) of degradation. 

The forced degradation experiments do not necessarily result in product decomposition. The study can be stopped if no degradation is observed after DS or DP has been exposed to a stress that exceeds conditions of accelerated stability protocol. Protocols for generation of product-related degradation may differ for DS and DP due to differences in matrices and concentrations. For example, sugar additives often present in DP are known to stabilize proteins vis-a-vis denaturing conditions. 

Under forcing conditions, decomposition products may be observed that are unlikely to be formed under the conditions used for confirmatory studies. This information may be useful in developing and validating suitable analytical methods. If in practice it has been demonstrated they are not formed in the confirmatory studies, these degradation products need not be further examined. 

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