论文部分内容阅读
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。
OBJECTIVE: To determine the equilibrium solubility of 10-methoxycamptothecin in different solvents and the apparent oil-water partition coefficients in n-octanol-water and n-octanol-buffer systems, and provide a reference for the design and preparation of new formulations. Methods: The equilibrium solubility of 10-methoxycamptothecin in different solvents and buffer solutions was determined by high performance liquid chromatography (HPLC). The equilibrium solubility of 10-methoxycamptothecin in n-octanol-water Apparent oil-water partition coefficient in buffer system. Results: The solubility of 10-methoxycamptothecin in 10 solvents and 8 pH buffers was determined. The equilibrium solubility of 10-methoxycamptothecin in water at 25 ℃ was 1.01 mg · L -1 , Better solubility in chloroform-methanol (1: 1), chloroform and methanol organic solvents; slightly increased equilibrium solubility in acidic buffer solution compared with water; equilibrium solubility in alkaline buffer solution pH value increased; the apparent partition coefficient of n-octanol / water of 10-methoxycamptothecin at 25 ℃ was 29.15 (lg P = 1.46), in the table of n-octanol / pH 1.0 phosphate buffer View of oil and water distribution coefficient larger [57.29 (lg P = 1.76)]. Conclusion: 10-Methoxycamptothecin is hardly soluble in water and slightly soluble in organic solvents such as methanol. Increasing the pH increases the solubility of 10-methoxycamptothecin, and 10-methoxycamptothecin has a larger oil-water partition coefficient under strongly acidic conditions.