双烟酸姜黄素酯平衡溶解度及表观油水分配系数的测定

Determination of Equilibrium Solubility and Apparent Oil-water Partition Coefficients of Nicotinate-curcumin Ester

目的:测定双烟酸姜黄素酯平衡溶解度和油水分配系数,为研究新剂型提供基础。方法:将双烟酸姜黄素酯分别溶解于pH1.2~7.8的缓冲溶液介质中,利用HPLC法定量分析,以饱和法测定双烟酸姜黄素酯的平衡溶解度,以摇瓶法测定正辛醇-水及缓冲盐溶液中双烟酸姜黄素酯的表观油水分配系数。结果:双烟酸姜黄素酯在pH6.8时的溶解度最大,双烟酸姜黄素酯的油水分配系数在pH1.2,pH5.8,pH6.5,pH7.8中lgP_(ap)值落在有利于体内药物的吸收范围(lgP_(ap)值为1.69~1.98)。但在其pH2.0,5.0,6.8时lgP_(ap)值大于2,亲脂性较强。结论:双烟酸姜黄素酯的平衡溶解度和表观油水分配系数与缓冲溶液介质的pH有关。在溶解度相对较大的pH下脂溶性较强,难以被人体吸收,需要进一步做剂型研究。

Objective： To determine the equilibrium solubility and the apparent oil/water partition coefficients of nicotinate-curcumin ester,so as to provide basis for the new formula design. Methods： Nicotinate-curcumin ester was dissolved in buffer solution with pH of 1. 2-7. 8. HPLC was used to detect the equilibrium solubility of nicotinate-curcumin ester in various solutions. The apparent oil/water partition coefficients in octanol-water and octanol-buffer solution system were measured by a shaking-flask method. Results： The solubility of nicotinate-curcumin ester in pH 6. 8 was the highest. The apparent oil-water partition coefficients of nicotinate-curcumin ester in pH 1. 2,5. 8,6. 5 and 7. 8 were lgP_（ap）values within the range（ lgP_（ap）= 1. 69-1. 98） beneficial to the absorption in vivo. But in pH 2,5 and 6. 8,the lgP_（ap）values were greater than 2 with strong lipophilicity. Conclusion： The equilibrium solubility as well as apparent oil/water partition coefficients of nicotinate-curcumin ester is greatly influenced by the pH value of media. In the pH value with relatively high solubility,lipophilicity is stronger,suggesting it is difficult to be absorbed by the body and needs to be further studied on dosage forms.