The phase diagrams for carbamazepine (CBZ) and nicotinamide (NCT) in ethanol and ethanol/ethyl acetate mixture were constructed at 298.15 K and 313.15 K under atmospheric pressure using the static method. The solubility of the 1:1 cocrystal is correlated as a function of the cocrystal former (nicotinamide) concentration by a mathematical model based on solubility product theory and the complexation process. The phase diagram of a CBZ–NCT cocrystal in pure ethanol at 298.15 K is asymmetric, which leads to an excess of coformer being needed to isolate the cocrystal. In terms of this issue, it was found that the solvent mixture can have a significant effect on the symmetry of phase diagrams. Employing solvent mixtures could make the phase diagrams of the CBZ–NCT cocrystal more symmetric and enlarge the safe operation region for the cocrystal. Additionally, in the cocrystal formation process, the nucleation of cocrystal and carbamazepine in a slurry crystallization, is a competitive relationship. For avoiding single component crystallization, the supersaturation ratio of cocrystal to drug should be increased to inhibit carbamazepine nucleation. These findings are all beneficial to the development of the cocrystallization process of the CBZ–NCT cocrystal.

中文翻译：

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298.15 K 和 313.15 K 乙醇和乙醇/乙酸乙酯混合物中卡马西平-烟酰胺共晶的三元相图研究

卡马西平 (CBZ) 和烟酰胺 (NCT) 在乙醇和乙醇/乙酸乙酯混合物中的相图是在 298.15 K 和 313.15 K 和大气压下使用静态方法构建的。通过基于溶度积理论和络合过程的数学模型，1:1 共晶的溶解度与共晶形成物（烟酰胺）浓度的函数相关。纯乙醇中 298.15 K 的 CBZ-NCT 共晶的相图是不对称的，这导致需要过量的共形成物来分离共晶。就这个问题而言，发现溶剂混合物对相图的对称性有显着影响。使用溶剂混合物可以使 CBZ-NCT 共晶的相图更加对称，并扩大共晶的安全操作区域。此外，在共晶形成过程中，共晶与卡马西平在浆液结晶中的成核是一种竞争关系。为避免单组分结晶，应增加共晶与药物的过饱和比以抑制卡马西平成核。这些发现都有利于CBZ-NCT共晶共结晶过程的发展。