A new approach to forced degradation studies using anhydrous conditions

Traditional forced-degradation experiments use aqueous solutions designed to address pharmaceutically relevant degradation mechanisms for drug substances. In general, the approach work well except in cases where the drug substance is a water-sensitive prodrug. A novel approach using anhydrous solutions to achieve similar types of degradation mechanisms was identified. In this article, the authors demonstrate that a normal-phase chromatographic method was stability-indicating for a water-sensitive prodrugs. The stress conditions using aqueous and non-aqueous conditions were also compared to understand the information obtained with each approach. Forced-degradation studies are crucial for demonstrating that drug-substance methods are stability-indicating. Traditional aqueous conditions may not be applicable for some molecules such as water sensitive products. Anhydrous conditions can be used in forced-degradation studies followed by normal-phase chromatography to demonstrate that the method is suitable for the determination of drug substance, impurities, and degradation products. Careful consideration must be given to the selection of anhydrous solvents, which must be compatible with the drug substance and reagents.