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Thermal and in Situ X‑ray Diffraction Analysis of a Dimorphic Co-Crystal, 1:1 Caffeine–Glutaric Acid

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journal contribution
posted on 10.02.2016, 16:41 by Venu R. Vangala, Pui Shan Chow, Martin Schreyer, Grace Lau, Reginald B. H. Tan
Spurred by the enormous interest in co-crystals from the pharmaceutical industry, many novel co-crystals of active pharmaceutical ingredients have been discovered in recent years, and this has in turn led to an increasing number of reports on polymorphs of co-crystals. Hence, a thorough characterization and understanding of co-crystal polymorphs is a valuable step during drug development. The purpose of this study is to perform in situ structural analysis and to determine thermodynamic stability of a dimorphic co-crystal system, 1:1 caffeine–glutaric acid (CA–GA, Forms I and II). We performed thermal and structural characterizations by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot-stage microscopy (HSM), and slurry and in situ variable temperature X-ray diffraction (VTXRD). For completeness, we have also redetermined crystal structures of CA–GA Forms I and II at 180 K using single crystal X-ray diffraction. Our results revealed that Form II is stable and Form I is metastable at ambient conditions. Further, the results suggest that the dimorphs are enantiotropically related and the transition temperature is estimated to be 79 °C.