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

• Published in: Chimia Vol. 79; no. 9; pp. 614 - 621
• Main Authors: Holzgrabe, Ulrike, Buschmann, Helmut, Handler, Norbert, Amer, Mostafa M., Hommelsheim, Renè, Beweries, Torsten, Bolm, Carsten
• Format: Journal Article
• Language: English
• Published: Switzerland Swiss Chemical Society 10.09.2025
• Subjects: Bulk Drugs; Drug Stability; Pharmaceutical Preparations - chemistry
• ISSN: 0009-4293; 2673-2424
• DOI: 10.2533/chimia.2025.614

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.