(517c) Pharmaceutical Precipitation on Amorphization and Process Characterization

Most pharmaceutical small molecules are developed as crystalline solids, as a crystalline API confers a number of advantages.  These advantages include enhanced chemical and physical stability, reproducibility and better processability which generally leads to crystalline solids being preferred over their poorly crystalline or non-crystalline counterparts.  However, the solubility and bioavailability of amorphous drug substances are increasingly compared with their crystalline counterparts during formulation development.  When these amorphous materials show enhanced exposure or stability characteristics, they can be of great interest to pharmaceutical development.

In this case study, the material characteristics and processability of the amorphous form of a model compound which intrinsically tends to form crystalline solvates were examined. This was accomplished through solution transformation from crystalline to amorphous solids.  Process knowledge leveraged from in-depth crystallization screening and process development provided insights on establishing appropriate conditions and boundaries for producing manageable amorphous material, and avoiding potential process hurdles such as de-mixing or poor filterability.  The findings and results that lead to a significant improvement in manufacturability and the selective particle engineering techniques applied will be presented.