Investigating the solubilization effect of oxcarbazepine by forming cocrystals
Investigating the solubilization effect of oxcarbazepine by forming cocrystals
复制标题
通过形成共晶体研究奥卡西平的增溶作用
DOI：
10.1039/c9ce00651f
复制
发表时间：
2019
期刊：
影响因子：
3.1
通讯作者：
Ren Zhongqi
中科院分区：
文献类型：
--
作者：
Li Xiangrong;Yu Guojia;Chen Xinjian;He Lichao;Zhou Zhiyong;Ren Zhongqi
奥卡西平(OXCBZ)是一种难于溶解的药物，不能形成盐。它的结构中含有酰胺官能团和羰基，可用于形成共晶体。采用液体研磨和反应结晶的方法成功地合成了三种OXCBZ共晶。由于OXCBZ含有一个酰胺基团和一个酮基，因此选择草酸(OA)、2，5-二羟基苯甲酸(2，5-DHBA)和水杨酸(SA)作为能与酰胺基或酮基形成氢键的异构体。通过粉末X射线衍射仪、差示扫描量热仪、热重分析、傅立叶变换红外光谱、扫描电子显微镜和固体核磁共振光谱对OXCBZ共晶的形成进行了表征。考察了不同条件对共晶制备的影响，优化了共晶制备工艺。考察了共晶体的表观溶解度和溶解速率。OXCBZ-OA和OXCBZ-2，5-DHBA共晶体的表观溶解度分别是纯药物的2.6倍和4.7倍。
Oxcarbazepine (OXCBZ) is a poorly soluble drug that can't form a salt. It has an amide functional group and a carbonyl group in its structure, which can be used to form cocrystals. Three cocrystals of OXCBZ were successfully synthesized through liquid-assisted grinding and reaction crystallization. Since OXCBZ has an amide group and a keto group, oxalic acid (OA), 2,5-dihydroxybenzoic acid (2,5-DHBA), and salicylic acid (SA) were selected as coformers which can form a hydrogen bond with an amide group or a keto group. The formation of OXCBZ cocrystals was confirmed by characterization via powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, and solid state nuclear magnetic resonance spectroscopy. Effects of different conditions on the preparation of the cocrystal were investigated to optimize the cocrystal preparation process. The apparent solubility and dissolution rate of the cocrystals were investigated too. The apparent solubility of the OXCBZ–OA and OXCBZ–2,5-DHBA cocrystals increased approximately 2.6 and 4.7 times that of the pure drug.