郁林娜,程盛勇,付洋,鲁文琴,黄静,罗喜荣,杨军
YU Linna,CHENG Shengyong,FU Yang,LU Wenqin,HUANG Jing,LUO Xirong,YANG Jun

• 1:贵州医科大学药学院
• 2:贵州医科大学
• 3:贵州医科大学附院药剂科
• 4:中国科学院地球化学研究所

摘要(Abstract)：

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Ultimate~? UPLC AQ-C_(18)(100 mm×2.1 mm,1.8μm),流动相为乙腈-水(45∶55),柱温30℃,检测波长210 nm。结果:37℃时诺米林在水中的平衡溶解度为14.12 mg/L,在二氯甲烷中溶解度最大为214 209.12 mg/L;诺米林的表观油水分配系数为131.05(lgP=2.12),在pH 3.0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(KeyWords)： 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
nomilin;equilibrium solubility;apparent oil/water partition coefficients;ultra performance liquid chromatography;bioavailability

Abstract:

Keywords:

基金项目(Foundation): 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]

作者(Author): 郁林娜,程盛勇,付洋,鲁文琴,黄静,罗喜荣,杨军
YU Linna,CHENG Shengyong,FU Yang,LU Wenqin,HUANG Jing,LUO Xirong,YANG Jun

DOI: 10.19367/j.cnki.1000-2707.2019.08.009

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