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, α and β. 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 °C the nucleation of the α-form from a clear aqueous solution occurred dominantly and nearly 100% α-form crystals were obtained. During the subsequent solvent-mediated transformation of the α-form crystals to the stable β-form, the α-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.