Abstract

Selecting the development form of an active pharmaceutical ingredient (API) in drug development is key to determining the final performance of the drug substance and drug product. Form selection requires an interdisciplinary approach involving a complex process to discover, monitor, and evaluate the solid-state characteristics, biopharmaceutical properties, stability, and processability of numerous forms. This Perspective discusses the importance of aligning critical material attributes with the desired quality target product profile to ensure drug safety and efficacy. It discusses how the form selection strategy is dependent on factors related to the administration route, dosage form, and therapeutic indication and provides an interdisciplinary framework with four prioritized sets of target attributes for oral delivery: solid-state properties, biopharmaceutical performance, stability, and processability. A classification system to guide form selection, particularly for immediate-release oral medications, is reviewed. The benefits of crystalline forms in terms of stability and processability are highlighted, emphasizing the role of solution crystallization in controlling their development. The interdisciplinary form selection process will be demonstrated through case studies highlighting how each set of target attributes were evaluated leading to the selection of ideal forms for development.

By Darren L. Reid, Margaret M. Faul, Vilmalí López-Mejías, Prashant Agarwal, Markus Bergauer, Laura E. Blue, Mary K. Chaves, John Chung, Melanie Cooke, Robert P. Farrell, James E. Huckle, Ron C. Kelly, Y.-H. Kiang, Weikun Li, Adrian Ortiz, Qiong Wu