Recent years have seen an increased thrust in process research and development toward developing continuous manufacturing processes for pharmaceutical and agrochemical molecules. To that end, we have been developing novel continuous crystallization schemes that facilitate increased throughput, improved process reliability, and reduced capital and operational costs. In this work we discuss a methodology we applied to design a continuous crystallization process for an agrochemical compound. Initial experimentation using an in-house MSMPR system uncovered challenges with the proposed process scheme, which typically resulted in plugging of lines and reactor deposits. Phase behavior considerations showed that the system is prone to oiling out. Subsequently, we developed a thermodynamic model to map out the various phase boundaries and used the knowledge of this phase diagram for finding the right conditions to operate the crystallizer stages. Plugging of lines and formation of deposits was avoided by adopting these new experimental conditions, and the process produced a product with desirable attributes. These results show the importance of focusing on the physical chemistry of the system while tackling the plugging-related challenges in a continuous crystallization process design and advance our understanding toward developing intensified continuous crystallization processes through experimental and modeling approaches.
