Comparative Evaluation of the Photostability of Carbamazepine Polymorphs and Cocrystals
Comparative Evaluation of the Photostability of Carbamazepine Polymorphs and Cocrystals
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DOI：
10.3390/cryst9110553
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发表时间：
2019-11-01
期刊：
影响因子：
2.7
通讯作者：
Fukami, Toshiro
中科院分区：
文献类型：
--
作者：
Yutani, Reiko;Haku, Ryotaro;Fukami, Toshiro
卡马西平 (CBZ) 是一种广泛使用的抗癫痫药，已知对光敏感。本研究的目的是评估用 D-65 荧光灯照射的三种 CBZ 共晶体（CBZ-琥珀酸 (SUC)、CBZ-糖精 (SAC) 形式 I 和 CBZ-SAC 形式 II）与传统固体形式（CBZ 多晶型物（形式 I、II 和 III））的光稳定性。使用比色测量确定的变色顺序与使用傅里叶变换红外反射吸收光谱估计的降解速率几乎一致，并且CBZ多晶型物的这些参数按照晶型III、晶型I和晶型II的顺序增加。与原始CBZ相比，CBZ-SUC和CBZ-SAC I型显着抑制CBZ的变色和降解，而CBZ-SAC II型则促进CBZ的变色和降解。这些结果得到了低频拉曼光谱结果的支持。使用固态核磁共振H-1自旋晶格弛豫时间估计的分子迁移率与降解速率常数密切相关，表明CBZ-SUC和CBZ-SAC I型形成后分子迁移率显着降低，并导致更高的光稳定性。总体而言，CBZ-SUC和CBZ-SAC I型是光稳定形式，共结晶被证明是提高光不稳定药物光稳定性的有效方法。
Carbamazepine (CBZ), a widely used antiepileptic, is known to be sensitive to light. The aim of this study was to evaluate the photostabilities of three cocrystals of CBZ (CBZ-succinic acid (SUC), CBZ-saccharin (SAC) form I, and CBZ-SAC form II) illuminated with a D-65 fluorescent lamp compared with those of the conventional solid forms: CBZ polymorphs (forms I, II, and III). The order of discoloration determined using a colorimetric measurement was almost consistent with that of the degradation rates estimated using Fourier-transform infrared reflection-absorption spectroscopy, and these parameters of CBZ polymorphs increased in the order of form III, form I, and form II. CBZ-SUC and CBZ-SAC form I significantly suppressed the discoloration and degradation of CBZ compared with the raw CBZ, while CBZ-SAC form II facilitated the discoloration and degradation of CBZ. These results were supported by the results from the low-frequency Raman spectroscopy. The molecular mobility estimated using solid-state nuclear magnetic resonance H-1 spin-lattice relaxation time strongly correlated with the degradation rate constant, indicating that molecular mobility significantly decreased following the formation of CBZ-SUC and CBZ-SAC form I and resulted in higher photostability. Overall, CBZ-SUC and CBZ-SAC form I are photostable forms and cocrystallization was proven to be an effective approach to improving the photostability of a photolabile drug.