Optimizing Solvent Selection and Processing Conditions to Generate High Bulk-Density, Co-Precipitated Amorphous Dispersions of Posaconazole
Derek S. Frank, Luke Schenck, Athanas Koynov, Yongchao Su, Yongjun Li, Narayan Variankaval
Abstract
Co-precipitation is an emerging method to generate amorphous solid dispersions (ASDs), notable for its ability to enable the production of ASDs containing pharmaceuticals with thermal instability and limited solubility. As is true for spray drying and other unit operations to generate amorphous materials, changes in processing conditions during co-precipitation, such as solvent selection, can have a significant impact on the molecular and bulk powder properties of co-precipitated amorphous dispersions (cPAD). Using posaconazole as a model API, this work investigates how solvent selection can be leveraged to mitigate crystallization and maximize bulk density for precipitated amorphous dispersions. A precipitation process is developed to generate high-bulk-density amorphous dispersions. Insights from this system provide a mechanistic rationale to control the solid-state and bulk powder properties of amorphous dispersions.