Simultaneous measurements of X-ray diffraction–differential scanning calorimetry: The investigation of the phase transition of ganciclovir and characterization of its polymorphic forms

Ganciclovir (GCV) is an antiviral drug for treating cytomegalovirus infections. This drug is reported to exist in four crystal forms in the solid state, with I and II being anhydrous and III and IV hydrates. Of particular interest about its thermal behavior, we performed simultaneous measurements of X-ray diffraction and differential scanning calorimetry (DSC) from a GCV commercial sample. The results showed that GCV Form III was stable between room temperature and ± 180 °C, and it transformed to Form I around 189 °C. Furthermore, the crystallization studies by slow solvent evaporation led to four GCV polymorphic forms (Form I, III, IV, and V), one anhydrous and three hydrated, respectively. GCV crystal forms were characterized by X-ray powder diffraction, thermogravimetry/derivative thermogravimetry, DSC, Fourier transform infrared spectroscopy and elemental analysis. Notable differences in the peak positions, shapes and intensities were detected. Slurry conversion experiments found that all recrystallized forms of GCV converted to Form I over time, consistent with Form I being the thermodynamically stable form. These results are relevant for the pharmaceutical development of GCV.