杨梅素-咖啡因共晶在不同有机溶剂中的形成热力学特征

Formation thermodynamics of myricetin-caffeine cocrystal in different organic solvents

目的考察了杨梅素-咖啡因共晶在甲醇、乙醇、丙酮中的形成热力学特征。方法通过测定杨梅素、咖啡因、杨梅素-咖啡因共晶在甲醇、乙醇、丙酮中的溶解度,探讨杨梅素-咖啡因共晶的溶液络合模型,计算相关热力学参数,并绘制3种溶剂的共晶三元相图。结果杨梅素-咖啡因共晶在3种溶剂中均符合1∶1溶液络合模型;共晶形成反应为热力学自发反应(ΔG°<0),随着温度升高,溶度积(Ksp)逐渐增大,络合常数(K11)逐渐减小,反应自发程度减弱,低温有利于共晶的形成;共晶的溶解为吸热过程(Δ_(sol)H_m>0),升高温度有利于共晶的溶解。杨梅素-咖啡因-溶剂(甲醇、乙醇和丙酮)三元体系的三相图为对称相图,共晶形成区域在乙醇和丙酮中较甲醇中大,共晶更易形成。结论利用热力学研究方法为选择共晶制备用溶剂及优化共晶制备条件奠定了理论和应用基础。

Objective To determine the effect of solvents on the formation thermodynamics of myricetin-caffeine（MYR-CAF） cocrystal. Methods Solubilities of MYR, CAF and MYR-CAF cocrystal in methanol, ethanol and acetone were determined and the complexation type of cocrystal in solvents was explored. Thermodynamic parameters of MYR-CAF cocrystal were calculated, including Gibbs free energy（ΔG）, enthalpy（ΔH）, entropy（ΔS） as well as enthalpy of solution（ΔsolHm）, and ternary phase diagrams（TPD） of the MYR-CAFsolvent systems were also plotted. Results ΔG° 0 indicated that the formation of MYR-CAF in the 3 solvents was a spontaneous process. The non-linear fitting demonstrated the 1∶1 complexation type for MYR and CAF in all 3 solvents. In addition, the increase of temperature resulted in the increase of Ksp and the decrease of K11 with lower degree of spontaneous reaction. Thus, low temperature favored the complexation between MYR and CAF and benefited the formation of MYR-CAF cocrystal. On the other hand, dissolving cocrystal was a endothermal process with the order of ΔsolHm as acetone methanol ethanol. All three TPDs of MYR-CAFsolvent systems were symmetric, and the larger cocrystal area occurred in ethanol and acetone related TPD, suggesting ethanol and acetone were the better solvent, for MYR-CAF cocrystal. Conclusion TPD and thermodynamic studies of MYR-CAF cocrystal provide a theoretical foundation for its further industrial production.