In situ monitoring of the solution-mediated polymorphic transformation of glycine: characterization of the polymorphs and observation of the transformation rate using Raman spectroscopy and microscopy

The aim of this work was to investigate the mechanism and progression of the solution-mediated polymorphic transformation and crystallization of glycine. The identification of the alpha- and gamma-forms of glycine crystals was performed using powder X-ray diffraction (PXRD), Raman microscopy and in situ probe Raman spectroscopy. The influence of the addition of NaCl and of the process parameters such as saturation temperature, seed size and stirring speed on the transformation behavior from the metastable alpha- form to the stable gamma- form was examined. In situ probe Raman spectroscopy was used to monitor the solid-phase properties - polymorphic composition. Fourier transform infrared spectroscopy (FTIR) with a ZnSe window was used to track the liquid-phase concentration at different times. Besides, the polymorphic transformation of glycine in the solvent was also examined in situ using a microscope with a heating/cooling stage. The integration of the different offline and in situ analytical measurement techniques greatly assisted in accurately and quantitatively perceiving the fundamental phenomena that govern the transformation process. Copyright (C) 2008 John Wiley & Sons, Ltd.