Predicting the photostability characteristics of active pharmaceutical ingredients using electron paramagnetic resonance spectroscopy

Objective: The purpose of this study was to determine if electron paramagnetic resonance (EPR) spectroscopy could be used to develop a quick method to predict the longer-term photostability characteristics of active pharmaceutical ingredients (APIs) for use in the early development phase. Materials and methods: EPR spectroscopy was used to study the photodegradation of nearly fifty different APIs in the solid state. Results: Free radical formation was detected in all but three of the APIs studied and singlet oxygen formation was also detected in the presence of five of the APIs tested. The extent of free radical formation in each API after 10 minutes exposed to light was used to rank the APIs in terms of their stability characteristics and determine the probable risk of photodegradation of the API during International Conference on Harmonisation (ICH) compliant photostability testing. A correlation was obtained between the extent of free radical formation on exposure to light and the known level of photodegradation products formed during ICH compliant testing. Conclusion: The EPR methods were shown to have the potential to predict the ICH level of photodegradation for an API in the solid state using only a small amount of sample and after just 10 minutes exposed to light. This testing can be performed in a shorter time frame than ICH compliant testing and can potentially be used early in development to predict the photostability characteristics of an API.