Challenges of Polymorphism Changes On Drug Substance and Drug Product Process Development - Case Study

Polymorphism of pharmaceutical compounds has broad impacts on drug substance and drug product development as the physical properties of the API and specifically of each polymorph may impact the formulation and pharmaceutical activity of the compound. Discovery of a more thermodynamically stable crystalline form creates challenges in both drug product and drug substance process development because of the API interaction with the formulation excipients and subsequent effect on the processing and stability of the drug product. This presentation will review the challenges following the discovery of a more stable polymorph, developing a robust API crystallization process that addresses the unique differences in crystal morphology and surface chemistry, and the interaction of drug substance properties on the processing and performance of the drug product.