Degradation conditions acid/base studies

Similar to accelerated studies, stress tests give a general picture of the chemical stability and degradation pathways under exaggerated conditions, such as under extreme pH conditions (acids and bases), heat, oxidative or reductive conditions, hydrolysis, and light irradiation (light irradiation tests at not less than 1.2 million lux hours are formalized as described in ICH QIB). These mostly non-formalized stress tests are only evaluated over a short term, e.g., 1 month. 

As these examples illustrate, historically there has been tremendous variation in the conditions employed in acid/base and oxidative stress testing studies. There has also been tremendous variation in defining the appropriate endpoint of the stress testing studies, i.e., what length of time (and temperature) or amount of degradation is sufficient to end the stress exposure. 

Purposeful degradation studies of the drug substance include appropriate solution and solid-state stress conditions (e.g., acid/base hydrolysis, heat, humidity, oxidation, and light exposure, in accordance with ICH guidelines). Guidelines from the United States Pharmacopoeia (USP), ICH, and FDA provide a brief outline of drug substance conditions. The ICH guidelines specifically state ... 

DP degradation cannot be predicted solely from the stability studies of the API in the solid state or solution. The non-APIs can also react with the API or catalyze degradation reactions. Impurities in the excipients can also lead to degradation in the DP not originally observed in the API. For solid oral DP formulations, heat, light, and humidity are often used as appropriate stress conditions. As indicated for API, DP stress conditions should result in approximately 5-20% degradation of the API or represent a reasonable maximum condition for a given formulation. The specific conditions used will depend on the chemical characteristics of the DP. For a solid DP, key experiments are thermal, humidity, and photostability. For solution formulations, additional experiments recommended in addition to thermal and photostability include acid/base hydrolysis and oxidation. 

Using similar conditions in another study [57] the weight loss of 55 pm films of a BTA-based copolyester containing approximately 55 mol% terephthalic acid was tested in the same kind of soil and was compared with the degradation of poly(e-caprolactone) (PCL Tone787, Union Carbide, films of 75 pm thickness) (Figure 10.5) in soil and in compost... 

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