Form Selection and Methods to Improve the Hygroscopic Behavior of the Selected Form

Polymorph and salt/cocrystal screens were conducted in order to select the most suitable form of an active pharmaceutical ingredient (API) for development.  Three forms including a hydrate, a channel solvate, and a cocrystal were discovered.  The channel solvate was the most promising form, although it showed unusual hygroscopic behavior during dynamic vapor sorption (DVS) analysis: when humidity increased from 50% to 60% relative humidity (RH), the crystal form quickly absorbed water and then slowly lost water and the residual organic solvent.  Various methods were explored to further understand the DVS behavior of the channel solvate and improve its physical properties.  It was shown that exposing the channel solvate crystals to water removed the residual organic solvents, reduced the water uptake, and improved its hygroscopicity.  The improved form was selected for further development.  The process to prepare the form with improved properties was successfully scaled up to multi-kilo batches.