Application of Wet Milling-Based Automated Direct Nucleation Control in Continuous Cooling Crystallization Processes

Abstract

A novel wet milling-based automated direct nucleation control (WMADNC) concept is proposed and implemented in two continuous cooling crystallization processes in this work. In process 1, WMADNC is implemented upstream to provide closed-loop controlled primary nucleation kinetics and produce seed crystals in situ for continuous mixed suspension mixed product removal crystallizer (MSMPRC). In process 2, WMADNC is applied downstream to achieve closed-loop controlled secondary nucleation kinetics and reduce particle size for crystals in the MSMPRC through recycling. For both processes, a focused beam reflectance measurement (FBRM)-based closed-loop control approach is successfully implemented to control the nucleation kinetics inside the wet mill therefore to control the final chord length distribution (CLD). In the proposed WMADNC approach, the process critical quality attributes (CQA) (e.g., particle number or size) can be directly controlled by the automated closed-loop control framework, which on one hand...