(226d) PAT Enabled Drying Platform for API Process Development – Investigation of Solvent Trapping Associated with Form Transition and Crystal Collapse during Drying

An active pharmaceutical ingredient was isolated as a crystalline hydrate which converts to an amorphous solid during drying. Challenges associated with material handling and incomplete drying were identified at the factory scale. It was suspected that differences in processing equipment and conditions were leading to rapid loss of water, collapse of the crystalline lattice, and trapping of the process solvent at levels above specification.

A PAT enabled drying platform was used and advanced laboratory methodologies were developed to capture detailed process data and gain a fundamental understanding of the drying process, test various theories for solvent trapping, and evaluate drying from an alternative solvent system. Experiments performed led to increased process understanding, identification of conditions needed for successful drying, and ultimate process selection to improve process efficiency, robustness, and portability. The newly developed process was successfully demonstrated at pilot plant scale with performance in line with model projections. Results of this investigation and the methods applied will be described in detail during this presentation.