Forced decomposition/degradation

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. 

As was the case for the forced-decomposition samples, the solid-state stability samples should be monitored using both PDA and MS detection to ensure that specificity of the candidate method is maintained. Analysis of the samples using an orthogonal method to further verify specificity is also recommended. If the method is, at this point, shown to provide separation among the API, all drug synthesis process impurities, and all degradation products, no additional method development is required at this juncture. When coelution is observed between components, development using additional column/mobile-phase combinations may be considered (see Section III.E). Alternatively, the use... 

Wood is an anisotropic material that undergoes uneven dimensional changes and, under extreme variations of environmental conditions, becomes distorted and warped (see Chapter 10). Exposed to the atmosphere, wood is also susceptible to the mechanical forces of wind and rain, and the effects of solar radiation the latter, in particular, causes discoloration initially, and then photochemical degradation, which often results in the wood s total decomposition. Wood is also prone to consumption by bacteria, fungi, insects, and rodent animals (Unger et al. 2001). 

To establish the degradation profile of a new drug, forced or stressed conditions such as hydrolysis, oxidation, photodegradation, and solid thermal decomposition are applied to the drug to generate degradation products that may be monitored by TLC or HPLC. 

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