Abstract Polymorphism in co-crystals is known to have a dramatic effect on physiochemical properties. The current contribution covers the characterization, thermodynamic analysis, and cooling seeded crystallization investigation of the urea-barbituric acid (UBA) polymorphic co-crystal system including urea (UA), barbituric acid (BA), and two polymorphic UBA (Forms I and III). Supramolecular synthesis of UBA Forms I and III have been conducted by cooling crystallization in methanol and then systematically characterized by powder X-ray diffraction (PXRD), thermal analysis (DSC and TGA), Raman and IR spectroscopy. Compared to the TGA results, the exothermic and endothermic peaks shown in DSC curves represent the decomposition of UBA and the melting of BA, respectively. Using the measured solubility data, the UBA polymorphs were found to be an enantiotropic polymorphic system, and the transition points in the water and methanol were determined at 35 °C and 33 °C, respectively. Subsequently, the modified Apelblat equation and van’t Hoff model were used to correlate the experimental data and to calculate the dissolution enthalpy and entropy of the different system. Moreover, cooling seeded crystallization of two polymorphic co-crystals in methanol was carried out to investigate the influence of process variables, such as seed amount, cooling rate, and stirring rate, on the crystal structure and crystal size distribution of final co-crystals.

中文翻译：

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尿素-巴比妥酸多晶型共晶体系：表征、热力学和结晶

摘要 已知共晶中的多晶现象对理化性质有显着影响。目前的贡献包括尿素-巴比妥酸 (UBA) 多晶型共晶系统的表征、热力学分析和冷却种子结晶研究，包括尿素 (UA)、巴比妥酸 (BA) 和两种多晶型 UBA（I 型和 III 型） ）。UBA I 型和 III 型的超分子合成是通过在甲醇中冷却结晶进行的，然后通过粉末 X 射线衍射 (PXRD)、热分析 (DSC 和 TGA)、拉曼光谱和红外光谱进行系统表征。与 TGA 结果相比，DSC 曲线中显示的放热和吸热峰分别代表 UBA 的分解和 BA 的熔化。使用测得的溶解度数据，发现 UBA 多晶型物是一个对映多晶型系统，水和甲醇中的转变点分别在 35 °C 和 33 °C 下确定。随后，使用修正的 Apelblat 方程和 van't Hoff 模型关联实验数据并计算不同系统的溶解焓和熵。此外，在甲醇中进行了两种多晶型共晶的冷却晶种结晶，以研究工艺变量，如晶种量、冷却速率和搅拌速率，对最终共晶的晶体结构和晶体尺寸分布的影响。修改后的 Apelblat 方程和 van't Hoff 模型用于关联实验数据并计算不同系统的溶解焓和熵。此外，在甲醇中进行了两种多晶型共晶的冷却晶种结晶，以研究工艺变量，如晶种量、冷却速率和搅拌速率，对最终共晶的晶体结构和晶体尺寸分布的影响。修改后的 Apelblat 方程和 van't Hoff 模型用于关联实验数据并计算不同系统的溶解焓和熵。此外，在甲醇中进行了两种多晶型共晶的冷却晶种结晶，以研究工艺变量，如晶种量、冷却速率和搅拌速率，对最终共晶的晶体结构和晶体尺寸分布的影响。