Polymorphism Control of l-Glutamic Acid in a Single-Stage and a Two-Stage MSMPR Crystallizer by Different Seeding Strategies

Abstract Control of polymorphism in continuous crystallization processes has been investigated. Using population balance modeling, we found that the relative growth and birth kinetics of different polymorphs play a major role on the steady-state polymorph outcome in a mixed-suspension mixed-product removal (MSMPR) crystallizer. In this communication, we present the conditions to harvest the desirable polymorph of l -glutamic acid (LGA) by numerical simulation and experimental observation in a two-stage MSMPR and a single MSMPR with intermittent seeding. Different polymorphic outcomes of l -glutamic acid can be achieved at different operating temperatures of the MSMPR crystallizer. The interplay of growth and nucleation kinetic makes the stable β-form hard to secure at low operating temperatures. The design of a two-stage MSMSPR crystallizer configuration with different working temperatures realizes the continuous seeding of the stable β form from the first MSMPR to the production crystallizer (second stage). Another approach to ensure the production of the desired polymorph is the use of intermittent seeding with the desirable polymorph to a single-stage MSMPR. The feasibility of both continuous seeding (in a two-stage MSMPR) and intermittent seeding (in a single stage MSMPR) strategies is demonstrated in this paper. Based on the l -glutamic acid crystallization kinetics, numerical simulation is used to figure out the best inlet concentration, working temperature, and intermittent seeding frequency for producing the desired yield and polymorph.