Quantitative measurement of the polymorphic transformation of L-glutamic acid using in-situ Raman spectroscopy

Control and optimization of the polymorph formation in batch crystallization processes require in-situ quantitative measurement of the concentration of different polymorphs. In this study, Raman spectroscopy was chosen to measure the polymorphic fraction of L-glutamic acid (L-Glu) in suspension. A sufficiently accurate calibration line was constructed using mechanical mixtures of the two forms, alpha and beta. The calibration line was also valid for the suspension system. The polymorphic behavior in batch cooling crystallizations of L-Glu was monitored using the calibration correlation. It was clearly observed by Raman spectroscopy that at 25 degreesC the nucleation of the alpha-form from a clear aqueous solution occurred dominantly and nearly 100% alpha-form crystals were obtained. During the subsequent solvent-mediated transformation of the a-form crystals to the stable alpha-form, the alpha-form fraction gradually decreased. The transformation rate has a strong temperature dependency so that the temperature increase promotes the transformation. Raman spectroscopy proved to be a powerful tool for measuring the polymorphic fraction in suspension.