Selecting and controlling API crystal form for pharmaceutical development--strategies and processes.

摘要

The success of designing, developing, manufacturing and introducing oral dosage forms of pharmaceutical products into the market relies on many steps, processes, stages and usually three phases of clinical trials. One key process is selecting an appropriate active pharmaceutical ingredient (API) crystal or amorphous form for the final dosage product: the ultimate goal of this selection process is to ensure that the manufactured product contains a stable and bioavailable active ingredient. A thorough knowledge of the solid-state chemistry of the API, the related excipients and the processes to make the product are critical in meeting this goal. Through recently published literature and the authors' experiences, this review describes the concepts and approaches that are used in the development of a truly knowledge-based crystalline API form selection process and highlights the appropriate studies which fit the Quality by Design (QbD) framework for pharmaceutical development activities. This review also discusses the potential API crystal form transformations in the API crystallization, post-crystallization and formulation stages, which are demonstrated by case study examples.