Drying an Organic Monohydrate: Crystal Form Instabilities and a Factory-Scale Drying Scheme to Ensure Monohydrate Preservation

This contribution discusses the laboratory results and factory-scale drying of an organic monohydrate with therapeutic qualities. The crystal form instabilities of this monohydrate are discussed with respect to undesired dehydrated crystalline species and an IPA solvate. To reproducibly determine the end-of-drying while ensuring deliverable monohydrate is produced, a factory-scale drying scheme in which a dew-point hygrometer is used to measure the water content of the dryer vapor effluent online was shown to be effective. This online measurement technique obviates the need for repeated sampling from the dryer and is a low-cost alternative to near-infrared (NIR) spectroscopy monitoring systems. This novel factory-scale drying scheme was successful in determining the end-of-drying while ensuring preservation of the desired monohydrate for four 20−30 kg batches. Also, drying curves were produced from the recorded dew-point data by an iterative approach.