(299a) Photochemical Models for Drug Substance Stability

The mathematical models generally utilized in process design of photochemical reactions can be readily implemented in the development of controls strategies for drug substances prone to photodegradation. We present here the development of two photochemical models used to quantify the risk to photodegradation of solid and liquid drug substance. A key feature of the model development is streamlined estimation of the relationship of the absorption spectra and the quantum yield to the wavelength of the incident light. The predictive power of the model enabled the design of a control strategy to limit the formation of the photodegradant. A methodology to minimize the experimental burden in the development of a mathematical model is proposed. Also presented are insights obtained from quantum mechanical modeling of the electronic transitions associated with the UV absorption spectra.