摘要 以茶碱、烟酰胺通过分子间氢键形成的共晶为例研究了共晶的热力学性质，测量了以异丙醇为溶剂茶碱烟酰胺共晶在298.15和308.15 K 下的溶解度，同时测定了茶碱烟酰胺共晶的溶度积（KSP）。通过对溶解度数据的分析表明茶碱烟酰胺共晶在溶液中会形成1∶1的溶液络合，测定了溶液中共晶的溶度积及络合常数以及共晶组元对共晶溶解度的影响，同时考察了温度对溶度积和络合常数的影响。为了深入了解共晶在不同温度下的形成规律，绘制了在298.15和308.15 K茶碱烟酰胺在异丙醇中的三元相图，分析了共晶的三元相图随温度的变化趋势，为药物共晶生产中目标产物的控制提供理论支持。
Abstract：
In this paper, the theophylline (TP)-nicotinamide (NCT) cocrystal formed by intermolecular hydrogen bond was used as an example for studying the thermodynamic analysis of cocrystal. The solubility and solubility product (Ksp) of theophyllinenicotinamide cocrystal in isopropanol were measured at 298.15 and 308.15 K at atmospheric pressure. The solubility data shows that significant complexation occurs in some solutions, and the relevant constant K11 is derived. The dependence of cocrystal solubility on the concentration of cocrystal components in solution were measured and explained by a cocrystal solubility product and by the binding constants of complexes formed in solution. The effect of temperature on solubility product and complex constant was also discussed. In order to investigate how the cocrystals crystallized at different temperature, the ternary phase diagrams for theophyllinenicotinamideisopropanol at 298.15 and 308.15 K were constructed and the variation tendency with temperature was discussed. The ternary phase diagrams help us understand how the cocrystal was crystallized from solution and provides theoretical basis for crystallization process.
GUO Jing-Jing, DANG Le-Ping, WEI Hong-Yuan.Solid-Liquid Phase Equilibrium and Phase Diagram for Ternary TheophyllineNicotinamideIsopropanol System at 298.15 and 308.15 K[J]. Chemcial Industry and Engineering, 2014,31(5): 49-53
2014, Vol. 31 
