(510f) Drying Mechanism and Aggregate Formation of API

After crystallization, the active pharmaceutical ingredient (API) isolated from a solvent/antisolvent system can form into hard aggregates during drying which could adversely affect drug product formulation. The objective of this study is to elucidate the mechanism of aggregate formation during drying of an API in the presence of a solvent/antisolvent system and to propose solutions to eliminate such formation. An integrated approach to understand and solve this problem was focused on 3 areas: crystallization, filtration/washing and drying. For the drying area, theoretical calculations were made to establish drying models that were verified experimentally with vapor concentration measurements made by mass spectroscopy and with drying curves formed by analyzing the wet cake weight change during drying. On the basis of these studies, pilot plant filtration/washing and drying protocols were modified which resulted in the elimination of hard aggregate formation. A mechanistic understanding of the formation of hard aggregates has wide applications to any API isolated from a solvent/antisolvent system.