Study of Batch and Semibatch Reactive Crystallization of <scp>l</scp> -Glutamic Acid with aid of PATs, focusing on Polymorphism and Crystal Habit

This work investigates the reactive crystallization of l-glutamic acid under different supersaturation generation strategies. Using PATs such as ATR-FTIR and in situ microscopes enables real-time monitoring of the supersaturation trajectory as well as the nucleation and growth behavior. In the batch process, crystallization starts instantaneously after the acid is added, leading to fines and clusters in the final products. Conversely, in the semibatch process, acid is dosed continuously, and more uniform α-LGA crystals are produced. The stochastic induction points were between the supersaturation range S_ind of 3 ∼ 5, and contributed to two distinct crystal habits. There seems to be a critical supersaturation level S_crt, specific for each certain dosing rate. If S_ind is higher than S_crt, it would enable faster transition of the generated nuclei to large sizes with lower tendency to agglomerate. If S_ind is below the value, it can not provide adequate driving force to allow the fast transition and lead to intergrown agglomerates. Moreover, it is found that applying ultrasound during the semibatch processes enhances the crystallization kinetics, making the induction points more reproducible, reducing the agglomeration, and affecting the competition of polymorphic forms. Integrating ultrasound into the hybrid batch/semibatch process could reduce the induction time and produce uniform and nearly pure α-LGA crystals.