(601a) Improvement of Drug Substance Bulk Powder Properties through Process Crystallization

The existing recrystallization process for a drug substance produced crystalline needle-shaped aggregates with low bulk and tap density and very poor flow properties. The particle properties led to poor performance of the drug substance during formulation. The goal of this work was to develop a process to yield drug substance with improved bulk powder properties for future formulation development and manufacturing work.

The approach taken for this work involved the use of computational and experimental solvent screens to rapidly narrow down the choice of solvent systems and working conditions. The computational work also had the advantage of significantly shortening development timelines.

Ultimately a crystallization process was developed which produced drug substance with enhanced particle morphology and significantly increased bulk density.