Modeling and Simulation of Antisolvent Crystallization: Mixing and Control

Abstract

This dissertation presents the development of simulation tools to address the issues of mixing and control in antisolvent crystallization processes, and to aid the development of systematic and scientific design approaches. The first part presents the development of an algorithm that couples macromixing and micromixing models with the population balance equation. It was applied to simulate antisolvent crystallization in a semibatch stirred vessel and an impinging jet crystallizer. The effects of the operational variables on the crystal size distribution and polymorphic form were numerically investigated. The second part focuses on the theoretical development and analysis of control strategies applied to antisolvent crystallization processes. For semibatch crystallization, the advantage of concentration control over specification of antisolvent addition rate was demonstrated by sensitivity analysis to process disturbances. For impinging jet crystallizers, it is shown that, by coupling with an aging vessel with controlled growth, specific crystal size distributions can be tailored.