(550b) A Case Study in Tuning API Powder Properties Via Crystallization to Meet Formulation Needs

Crystal form and powder properties are universal quality attributes which characterize every API. This presentation is a case study of one API that has the potential to form numerous polymorphs and a variety of crystal morphologies. Process development efforts were focused on obtaining the thermodynamically stable crystal form while targeting a narrow range of powder properties suitable for bioavailability and downstream drug product formulation. The work includes screening studies to select the appropriate solvent system and crystallization parameter optimization to control particle size and minimize agglomeration. Multiple technologies were employed to support this work, including FTIR, FBRM, wet milling, and dry milling. Understanding the impacts of crystallization parameters allowed for the generation of several lots of material with a variety of powder properties, which were evaluated for formulation behavior and bioavailability. The feedback and collaboration between drug substance and drug product process development teams enabled the selection of the desired target material properties (eg. particle size distribution, D90/D50 ratio) and formulation process (roller compaction or wet granulation) that would robustly lead to high quality drug to patients.