10-甲氧基喜树碱平衡溶解度和表观油水分配系数的测定

Determination of Equilibrium Solubility and Apparent Oil/Water Partition Coefficient of 10-methoxycamptothecin

摘要:

目的：测定10-甲氧基喜树碱在不同溶剂中的平衡溶解度以及在正辛醇-水和正辛醇-缓冲液体系中的表观油水 分配系数，为新型制剂的设计和制备提供参考。方法：采用高效液相色谱法（HPLC）测定10-甲氧基喜树碱在不同溶剂和缓冲溶液中的平衡溶解度；采用摇瓶法测定10-甲氧基喜树碱在正辛醇-水/缓冲液体系中的表观油水分配系数。结果：确定了10-甲氧基喜树碱在10种溶剂和8种pH的缓冲溶液中的溶解度，25 ℃时10-甲氧基喜树碱在水中的平衡溶解度为1.01 mg·L^-1，在三氯甲烷-甲醇（1：1）、三氯甲烷及甲醇有机溶剂中溶解性较好；在酸性缓冲溶液中的平衡溶解度较水中略有增加；在碱性缓冲溶液中的平衡溶解度随pH增强而增加；25 ℃时10-甲氧基喜树碱的正辛醇/水的表观分配系数为29.15（lg P=1.46），在正辛醇/pH 1.0的磷酸盐缓冲液中表观油水分配系数较大[57.29(lg P=1.76)]。结论：10-甲氧基喜树碱难溶于水而微溶于甲醇等有机溶剂。增大pH可增加10-甲氧基喜树碱的溶解度，在强酸性条件下10-甲氧基喜树碱有较大的油水分配系数。

Abstract:

Objective: To determine equilibrium solubility of 10-methoxycamptothecin (10-MCPT) in various media and its partition coefficients for the n-octanol-water/buffer solution systems which would settle fundament for the design and manufacture of a new dosage form. Method: HPLC was used to determine equilibrium solubilities of 10-MCPT. Using shake flask method determination of 10-MCPT in octanol-water/buffer liquid apparent oil-water partition coefficient of system. Result: For the first time 10-MCPT in 10 kinds of solvents and pH buffer solution of solubility were identified, at 25 ℃ when the 10-MCPT equilibrium solubility in water of 1.01 mg·L^-1, the chloroform-methanol 1:1, chloroform and methanol had good solubility in organic solvents. The equilibrium solubility in acid buffer solution was a slight increase in water;in alkaline buffer solution of the equilibrium solubility increases with pH increased;at 25 ℃ 10-MCPT was octanol/water apparent partition coefficient of 29.15 lg (P=1.46), are in octanol/pH 1.0 apparent oil-water partition coefficient is larger in the phosphate buffer [57.29]lg (P=1.76). Conclusion: 10-MCPT poorly soluble in water and slightly soluble in methanol and other organic solvents. Increases of the pH can increase the solubility of 10-MCPT, under the condition of strong acid 10-MCPT have larger oil-water partition coefficient.