Process kinetics and regulation in reactive crystallization: Polymorphic control and morphology optimization for enhancing powder properties of thiothiamine

The important intermediate thiothiamine for Vitamin B1 production is often challenged by issues related to mixed polymorphs and needle-shaped crystal morphology in industrial production. These challenges can be effectively addressed through crystal engineering strategies. In this study, the key factors affecting the crystal form were investigated in reactive crystallization. Subsequently, the reactive crystallization process was monitored online using in-situ ATR-FTIR and FBRM techniques. It was determined that crystallization process is the rate-limiting step throughout the reactive crystallization process. Various factors affecting the crystal morphology were identified. Through process control and optimization, a product was achieved with a filtration time reduced by over 60% and a moisture content reduction of >20%. Overall, this study provides valuable insights from a crystal engineering perspective to address the poor powder properties.