Cold-crystallization and physical stability of glassy carbamazepine
Cold-crystallization and physical stability of glassy carbamazepine
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DOI：
10.1016/j.tca.2021.179100
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发表时间：
2021-11-15
影响因子：
3.5
通讯作者：
Zielinski, Piotr M.
中科院分区：
文献类型：
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作者：
Dolega, Agnieszka;Juszynska-Galazka, Ewa;Zielinski, Piotr M.
采用粉末X射线衍射仪(XRD)、差示扫描量热仪(DSC)和傅立叶变换红外光谱(FT-IR)对急冷药物卡马西平(CBZ)的物理稳定性以及等温和非等温冷结晶进行了研究。报道了玻璃在加热过程中发生的三个相变：软化(329K)、冷结晶(389K)和熔化(463K)。利用Adam-Gibbs模型对CBZ非晶态样品进行了分析，结果表明，CBZ非晶态样品在室温下(低于玻璃化转变温度约30K)保持了8h的物理稳定性。等温X射线衍射测量表明，即使在玻璃化转变温度约50K以下，非晶态CBZ也容易快速形核，但在此条件下晶体生长会明显减慢。计算了脆性参数m，确定急冷CBZ为中脆性玻璃。FT-IR测量与移动窗口二维相关光谱相结合证明了振动动力学的变化伴随着所有的相变。在冷结晶过程中观察到氢键的显著加强。
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.