诺米林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 Nomilin

作　　者：郁林娜 程盛勇 付洋 鲁文琴 黄静 罗喜荣 杨军[3] YU Linna;CHENG Shengyong;FU Yang;LU Wenqin;HUANG Jing;LUO Xirong;YANG Jun(School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, Guizhou, China;Department of Pharmacy, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou;Institute of Geochemistry, Chinese Academy of Sciences, Guiyang 550081, Guizhou, China)

机构地区：[1]贵州医科大学药学院,贵州贵阳550025 [2]贵州医科大学附院药剂科,贵州贵阳550004 [3]中国科学院地球化学研究所,贵州贵阳550081

出　　处：《贵州医科大学学报》2019年第8期912-915,共4页Journal of Guizhou Medical University

基　　金：贵州省科学技术基金项目[黔科合J字(2013)2037];贵州省社发攻关项目[黔科合SY字(2015)3032];贵州省联合基金项目[黔科合LH字(2014)7091]

摘　　要：目的:测定诺米林的平衡溶解度及表观油水分配系数,为其剂型设计提供依据。方法:采用摇瓶法和超高效液相色谱法(UPLC)测定诺米林有机溶剂、表面活性剂及磷酸盐缓冲液的平衡溶解度,观察正辛醇-水/磷酸盐缓冲液中的表观油水分配系数,色谱柱为UltimateUPLCAQ-C18(100mm×2.1mm,1.8μm),流动相为乙腈-水(45∶55),柱温30℃,检测波长210nm。结果:37℃时诺米林在水中的平衡溶解度为14.12mg/L,在二氯甲烷中溶解度最大为214209.12mg/L;诺米林的表观油水分配系数为131.05(lgP=2.12),在pH3.0缓冲液中表观油水分配系数最大为783.07(lgP=2.89);十二烷基硫酸钠(SDS)对诺米林具有较强的增溶能力。结论:诺米林水溶性差,但渗透性较好,适合制成口服制剂。Objective: To determine the equilibrium solubility of nomilin and the apparent oil-water partition coefficient (AOWPC) for providing rationales for designing its dosage form. Methods: Shake flask method and ultra performance liquid chromatography (UPLC) were used to measure the equilibrium solubility of nomilin in different media such as organic solvent,water,buffer solutions,surfactant solutions.Nomilin AOWPC in the octanol-water/buffer was measured.UPLC settings were listed below: Ultimate? UPLC AQ-C18 column (100 mm×2.1 mm,1.8 μm),acetonitrile- water (45:55) as the mobile phase,the column temperature at 30 ℃,and the detection wavelength at 210 nm. Results: At 37 ℃,the equilibrium solubility of nomilin was 14.12 mg/L in water and its maximum was 214 209. 12 mg/L in dichloromethane. The AOWPC of nomilin was 131.05(lgP=2.12 ) in the octanol-water system,while its largest value was 783.07 ( lgP=2.89 ) in pH 3.0 buffer solution system.Sodium dodecyl sulfate (SDS) was a good solvent for nomilin. Conclusion: Nomilin is poorly soluble in water,but strongly permeable.Therefore nomilin is suitable for oral preparation.

关 键 词：诺米林 平衡溶解度 表观油水分配系数 超高效液相色谱法 生物利用度 

分 类 号：R917[医药卫生—药物分析学]