姜黄素-邻苯二酚共晶溶度积的研究

Research on Solubility Products of Curcumin-catechol Co-crystal

关键词:  姜黄素  邻苯二酚  共晶  溶度积

Key words:  curcumin  catechol  co-crystal  solubility products

摘要:

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（K₁₁）。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，K₁₁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。

Abstract:

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 (K₁₁).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 K₁₁ 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.