Form Conversion and Solvent Entrapment during API Drying

An active pharmaceutical ingredient (API) was isolated from solution as a crystalline hydrate and then converted to the desired weakly crystalline form during drying. Incomplete solvent removal was observed at the factory scale. It was suspected that differences in the processing equipment and drying conditions led to the rapid loss of water from the solids, early form conversion, and subsequent trapping of the process solvent above specification levels. Experiments were conducted to gain a better understanding of the drying process and test theories for solvent trapping. The practical methods and techniques described here are considered broadly applicable to API drying process development; findings associated with solvent entrapment may be common across compounds undergoing a form transition during drying. This article presents experimental results that led to an increased process understanding and identification of conditions for successful drying of the API.