Cold-crystallization and physical stability of glassy carbamazepine

Physical stability as well as isothermal and non-isothermal cold-crystallization of quench-cooled drug carbamazepine (CBZ) was studied using powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FT-IR). Three phase transitions on heating were reported: glass softening (similar to 329 K), cold-crystallization (similar to 389 K) and melting (similar to 463 K). XRD results and evaluation of DSC data using Adam-Gibbs model extended to the glassy state revealed, that the amorphous sample of CBZ remains physically stable for 8 h at room temperature (i.e. about 30 K below glass transition temperature). Isothermal XRD measurements showed that amorphous CBZ is prone to rapid nucleation even about 50 K below the glass transition, but crystal growth is considerably slowed down in such conditions. Fragility parameter m was calculated and quench-cooled CBZ was identified as moderately fragile glass. FT-IR measurements coupled with moving-window two-dimensional correlation spectroscopy proved that changes in vibrational dynamics accompanied all phase transitions. Considerable strengthening of hydrogen bonding was observed during cold crystallization.