Effect of Fluid Flow on Crystallization in a Segmented Flow Microchannel

Abstract

Segmented flow crystallization has attracted the attention of engineers in the development of drug substance processes, because the crystallization behavior is different from that observed in conventional stirred tanks. Under segmented flow conditions, the crystal size distribution is narrower, and the crystallization rate is higher than that of batch crystallization. However, the phenomenological theory of segmented flow crystallization has not been clarified. The purpose of this study was to gain more insights into segmented flow crystallization phenomena. We focused on the influence of fluid behavior on crystallization. First, we analyzed the motion of crystals in a segmented flow using computational fluid dynamics. Under the assumption that the mass transfer is the rate-determining step of crystal growth, we evaluated how particle and flow conditions contribute to the mass transfer. The shear rate under segmented flow was found to be approximately 16 times greater than that in a stirred tank. The high shear rate induced a high mass transfer rate, which is often observed under segmented flow conditions.