Humidity-driven Polymorph Control during Industrial Drying of Ivabradine Hydrochloride

The present work describes the development of a scalable process for the preparation of Ivabradine hydrochloride, in two different polymorphic forms, known as δ-dry and β. Extensive solid-state analyses enabled the identification of key relative humidity thresholds that govern phase transitions. On this basis, an optimized drying protocol was developed, giving efficient desolvation while maintaining controlled hydration levels. The process was successfully validated at kilogram scale, affording both polymorphic forms with high reproducibility. This work highlights the crucial role of humidity control in the large-scale production of polymorphic APIs.