New Bench-Scale Method To Elucidate Active Pharmaceutical Ingredient Drying Mechanisms

Drying of an active pharmaceuticalingredient, in theform of acrystalline hydrate, was investigated using a small-scale flow cellmethodology. A new laboratory tool was developed and demonstratedusing a simple segregated column technique to quickly distinguishdifferent drying mechanisms using a minimal number of experiments.For the case studied here, increasing vacuum levels improved the removalof solvents while use of nitrogen flow through the solids facilitatedwater removal. Additional results are presented from experiments conductedto assess the impact of the crystallization solvent system and washingon drying behavior and cake properties. A system was identified whichavoided issues associated with poor cake handling and improved overalldrying performance. This article provides details on the new experimentalmethod used that helped lead to the rapid development of an improveddrying process and presents results demonstrated through the pilotplant scale.

Automated summary

Drying of a crystalline hydrate form of an active pharmaceutical ingredient was studied using a small-scale flow cell methodology. A new experimental tool was developed, which used a segregated column technique to quickly identify different drying mechanisms with minimal experiments. The results showed that increasing vacuum levels improved solvent removal, while nitrogen flow through the solids facilitated water removal. The impact of crystallization solvent system and washing on drying behavior and cake properties were also assessed, and a system that improved drying performance was identified.