Multiscale Modeling and Simulation of Macromixing, Micromixing, and Crystal Size Distribution in Radial Mixers/Crystallizers

Abstract

Continuous-flow tubular crystallization in which seed crystals are continuously generated is of interest due to its enabling of tighter control of crystal properties. This article is the most detailed simulation study on the design and operation of continuous-flow crystallizers using radial mixers, which have potential for inducing rapid and intense turbulent mixing and having easy construction, high reliability, and low operating costs. A multiscale model is employed that couples computational fluid dynamics (CFD), micromixing modeling, energy balance, and population balance equation (PBE) using the open-source CFD package OpenFOAM. The approach is demonstrated for the methanol–water antisolvent crystallization of lovastatin. A new crystallizer design with multiple radial inlets is proposed and shown to deliver improved mixing compared to one radial inlet. The effects of varying operating conditions on micromixing and crystal size distribution are analyzed. A systematic approach is provided for the desig...