Cold-crystallization and physical stability of glassy carbamazepine

• Published in: Thermochimica acta 2022-01, Vol.707, p.179100, Article 179100
• Main Authors: Dołęga, Agnieszka, Juszyńska-Gałązka, Ewa, Deptuch, Aleksandra, Baran, Stanisław, Zieliński, Piotr M.
• Format: Article
• Language: English
• Subjects: Carbamazepine; Cold-crystallization; Differential scanning calorimetry; Fourier-transform infrared spectroscopy; Moving-window two-dimensional correlation spectroscopy; X-ray diffraction
• ISSN: 0040-6031; 1872-762X
• DOI: 10.1016/j.tca.2021.179100

•Quench-cooled carbamazepine is unstable when stored at room temperature.•Physical stability is significantly improved when stored in refrigerator.•Calculated relaxation times may not properly reflect physical stability.•Changes in vibrational dynamics reflect all observed phase transitions.•The most significant changes in dynamics accompany cold crystallization. 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 (∼329 K), cold-crystallization (∼389 K) and melting (∼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.