S. Swain, Vivek V. Ranade
In this work, hydrodynamic cavitation (HC) was used to enhance nucleation and intensify continuous antisolvent crystallization processes. The influence of vaporous cavities and nano-/microbubbles generated through HC and aeration on nucleation was first investigated using induction time measurements. Two model systems, carbamazepine-ethanol-water (CBZ-EtOH-H2O) and paracetamol-methanol-water (PCM-MeOH-H2O), were considered. HC reduced the characteristic induction time for both systems, with a further reduction observed in the presence of air. Correlations describing the influence of supersaturation on induction time were developed for both systems. Based on these findings, a novel continuous cavi-crystallization configuration was developed in which the active pharmaceutical ingredient (API) containing stream was not directly exposed to cavitation. The developed configuration was evaluated using the PCM-MeOH-H2O system in a continuous oscillatory baffled crystallizer (COBC). A generalized tanks-in-series population balance model (PBM) was used to simulate the steady-state behavior of the COBC system. The presence of cavitation-generated bubbles reduced fouling/ encrustation, and enhanced nucleation, crystal growth, the characteristic crystal size, crystal yield and productivity. The developed approach provides a new pathway for leveraging HC to realize intensified and scalable continuous antisolvent crystallization processes with enhanced productivity and reduced fouling