457998 Case Study of a Recrystallization Scale-up with Desirable Psd and Morphology
Efforts began with a solvent screen and construction of solubility curves, using the Avantium Crystal16™ parallel crystallizer. Experiments were conducted at the 100 mL scale using the Mettler Toledo EasyMax™ workstation to optimize dosing and cooling strategies. In situ FBRM and PVM probes were used.
The most promising conditions were then tested at the 2 L scale, using the Mettler Toledo RC1e™. CFD mixing modeling was used to achieve a greater understanding of the effects of mixing regimes on the results of the 2 L recrystallization; this was then used to project the effects of mixing at larger scales up to the target reactor volume of 200 gallons. In addition, FBRM and IR data were used to construct desaturation curves, which aided in reducing the batch cycle time without negatively impacting the crystallization. The 2-L RC-1 resulted in yields greater than 90% and gave isolated solids with improved thermal stability, while meeting the target morphology and size requirements. This process was then used to scale up the crystallization to a 20 L vessel, and finally, to 200 gallons.