Process Performance and Operational Challenges in Continuous Crystallization: A Study of the Polymorphs of L-Glutamic Acid

[Image: see text] The crystallization of the two polymorphs of l-glutamic acid (LGA) is carried out in a continuous crystallization process, and its performance according to different criteria is evaluated. The study aims at identifying suitable operating conditions for producing either αLGA or βLGA with a high polymorphic purity. To this end, we investigate the process both from a theoretical perspective and through experiments using either a single stirred-tank crystallizer or a cascade of two stirred-tank crystallizers in series. In terms of theory, we extend the MSMPR-based steady-state stability analysis of Farmer et al. (Farmer, T. C. et al. AIChE J.2016, 62, 3505–3514) by accounting for the possibility of a nonrepresentative withdrawal of the solid phase from the crystallizer. Additionally, the process is simulated using population balance equations, thereby investigating the effect of operating conditions on polymorphic purity, yield, and productivity. Guided by the model-based conclusions, we identified suitable operating conditions and experimentally tested them. The experimental campaign has demonstrated that βLGA could be successfully and continuously produced in both process configurations according to the theory with performance as expected, whereas that was not possible for αLGA. The difference between the two stems from different operational challenges, whose consequence is that steady-state operation is attained in the case of βLGA but not in that of αLGA. In the former case, the needle-like βLGA crystals, which exhibit no agglomeration, tend to be only slightly oversampled; in the latter case, the prismatic αLGA crystals undergo major agglomeration and hence are very difficult to suspend and effectively withdraw from the crystallizer.