姜黄素-邻苯二酚共晶溶度积的研究

Research on Solubility Products of Curcumin-catechol Co-crystal

目的以姜黄素为药物活性成分,邻苯二酚为共晶形成物,研究姜黄素-邻苯二酚共晶在不同溶剂(甲醇和乙酸乙酯)中和不同温度下形成的热力学。方法通过固态研磨法制备姜黄素-邻苯二酚共晶,并用X射线衍射表征,测定其在不同溶剂(甲醇、乙酸乙酯)、不同温度下的溶解度,采用络合模型计算共晶的溶度积(K_(sp))和络合常数(K_(11))。结果姜黄素-邻苯二酚共晶在甲醇溶剂中符合1∶1溶液络合模型,随着温度的升高,K_(sp)逐渐增大,K_(11)逐渐减小。在乙酸乙酯溶剂中符合无溶液络合模型,K_(sp)随温度升高而逐渐增加。结论比较共晶在2种溶剂中的溶度积,发现其在甲醇中容易络合。该热力学研究为姜黄素-邻苯二酚共晶的制备条件优化奠定了一定的理论和应用基础。

OBJECTIVE To investigate the thermodynamics of curcumin-catechol co-crystals in which curcumin was used as the active pharmaceutical ingredient and catechol as the co-crystal conformer,in different solvents（methanol and ethyl acetate）and different temperature.METHODS Co-crystal was prepared by solid state grinding method,and characterized by X-ray diffraction.Solubility of curcumin-catechol co-crystals in different solvents（methanol and ethyl acetate solvent）and various temperatures were measured,followed by fitting the complexation model to calculate solubility products（K（sp））and complexation constants（K（11））.RESULTS Based on the non-linear simulation,1∶1 complexation model was well fitted to the curcumincatechol co-crystal formation in methanol,while no complexation model was more suitable for that in ethyl acetate.The data K（sp ）increased while K（11 ）decreased with the reaction temperature.CONCLUSION The co-crystal is easily complexable in methanol when compared the co-crystal solubility products in two solvents.This thermodynamic study has provided a theoretical and applied foundation for the preparation and optimization of curcumin-catechol co-crystal.