Insight into thermally induced solid-state polymorphic transformation of sulfathiazole using simultaneous in situ Raman spectroscopy and differential scanning calorimetry

Pharmaceutical solids exposed to thermal stress during manufacturing processes undergo various phase transformations in bulk drug substances or excipients, resulting in altered dosage form performance. Due to its relatively rapid spectral acquisition rate, as well as the possibility of incorporation into in-line monitoring, Raman spectroscopy is ideally suited to monitoring the transformation between different solid-state forms. In this study, we demonstrate that the transition temperature for polymorphs can be estimated from the transformation profiles obtained from real-time, in situ, simultaneous Raman spectroscopic, and differential scanning calorimetric data. Using this method, we have estimated the transition temperature of the solid-state transformation of the enantiotropically related sulfathiazole polymorphs III and I. These results suggest that this method is a useful approach to determine transition temperatures in systems that are not amenable to accessing other methods. Copyright (C) 2009 John Wiley & Sons, Ltd.