Biological Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gujarat, 382355, India.
Chemical Engineering, Indian Institute of Technology Gandhinagar, Palaj, Gujarat, 382355, India.
AAPS PharmSciTech. 2021 Jan 6;22(1):29. doi: 10.1208/s12249-020-01888-6.
In this work, carbamazepine (CBZ), an anticonvulsant drug was cocrystallized with several structurally complement coformers (coformers with amide, acid and hydrazide functional groups) to enhance its dissolution. CBZ formed a cocrystal phase with acetamide (ACE) when mixtures of CBZ and ACE (containing CBZ mole fractions, X of 0.25, 0.33, 0.5, and 0.67) were subjected to solid-state grinding (SSG), evaporative crystallization (EC), slurry conversion (SC), and slow cooling crystallization (SLC). Upon heating, the CBZ-ACE cocrystal phase formed from CBZ-ACE mixtures containing X of 0.25, 0.33 and 0.67 underwent solid-state phase transition to CBZ form I and CBZ cocrytsal phase obtained from the CBZ-ACE mixture containing X of 0.5 converted to CBZ form III. Interestingly, slow cooling cocrystallization experiments resulted in crystallization of a cocrystal as well as the CBZ dihydrate forms. The powder dissolution studies demonstrated that among the different CBZ-ACE-SSG cocrystal phases, CBZ-ACE-SSG-X-0.33 cocrystal exhibited 7.47 times improved dissolution whereas the CBZ eutectic phase with nicotinic acid hydrazide (NAH) exhibited 4.93 times increased dissolution when compared to raw CBZ.
在这项工作中，抗惊厥药物卡马西平（CBZ）与几种结构互补的共晶形成剂（具有酰胺、酸和酰肼官能团的共晶形成剂）共结晶，以提高其溶解性能。当 CBZ 和乙酰胺（ACE）的混合物（含有 CBZ 摩尔分数 X 为 0.25、0.33、0.5 和 0.67）进行固态研磨（SSG）、蒸发结晶（EC）、浆料转化（SC）和缓慢冷却结晶（SLC）时，CBZ 与 ACE 形成共晶相。加热时，由 X 为 0.25、0.33 和 0.67 的 CBZ-ACE 混合物形成的 CBZ-ACE 共晶相经历固态相转变为 CBZ 形式 I 和由 X 为 0.5 的 CBZ-ACE 混合物获得的 CBZ 共晶相转变为 CBZ 形式 III。有趣的是，缓慢冷却共结晶实验导致共晶以及 CBZ 二水合物形式的结晶。粉末溶解研究表明，在不同的 CBZ-ACE-SSG 共晶相中，CBZ-ACE-SSG-X-0.33 共晶显示出 7.47 倍的溶解提高，而与烟酸酰肼（NAH）的 CBZ 共熔相显示出 4.93 倍的溶解提高，与原始 CBZ 相比。
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