Mechanochemical Degradation of Active Pharmaceutical Ingredients (APIs): A Simple Tool for the Prediction of Drug Stability.

Abstract

Knowledge of the potential degradation products of active pharmaceutical ingredients (APIs) is of major interest for the development and approval of new drugs. Therefore, methodologies for the time-efficient and precise prediction of degradation products and pathways are of great importance. Traditional degradation assessments typically involve solution-based forced degradations under acidic, basic, thermal, or photolytic conditions. However, such conditions often fail to accurately replicate degradation pathways relevant to solid-state formulations. A promising addition to the established solvent-based approaches are forced degradation processes in the solid-state using mechanochemistry. The newly developed methodologies enable a time-efficient and accurate simulation of degradation pathways under mild reaction conditions in the solid-state. Herein, the general principles of forced mechanochemical degradations will be discussed on the basis of published case studies involving marketed drugs.