大黄酸平衡溶解度和油水分配系数的测定
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摘要
目的测定大黄酸在不同溶剂中的平衡溶解度及表观油水分配系数,为大黄酸新剂型的设计提供参考依据。方法采用高效液相色谱法测定大黄酸在水、不同p H值缓冲液、不同溶剂中的溶解度;采用经典摇瓶法测定大黄酸在正辛醇缓冲液中的表观油水分配系数。结果 37℃时大黄酸在水中的平衡溶解度为3.89μg·m L~(-1),表观油水分配系数(lgP)为2.79;大黄酸的溶解度在随着p H值的升高呈现增加的趋势,在p H值6.8和7.4的磷酸盐缓冲液中分别达362.20和431.65μg·m L~(-1)。大黄酸在半极性溶剂中溶解度相对较好,特别是在聚乙二醇400中的溶解度可达2 971.74μg·m L~(-1)。大黄酸的油水分配系数随p H值的升高而下降,在p H值6.8和7.4的磷酸盐缓冲液中分别为0.83和0.54。结论大黄酸水溶性差,增大p H值可增加其溶解度,但油水分配系数随之降低。
Objective To determine the solubility of rhein in different vehicles and its partition coefficients in the noctanol-water system for designing new formulations. Methods High performance liquid chromatography( HPLC) method was established to determine the concentration of rhein in water,different p H solutions and different solvents; the partition coefficients for the n-octanol-buffer solution systems were determined by shaking flask method. Results The equilibrium solubility of Rhein was 3.89 μg·m L-1 and the lg P was 2.79 in water at 37 ℃. The solubility of rhein was increased with the raise of p H,which could reach 362.20 and 431.65 μg·m L-1 in phosphate buffer solution at p H 6.8 and 7.4,respectively.Solubility of rhein in the semi polar solvent was relatively good,which can up to 2 971.74 μg·m L-1 in PEG400.The oil-water partition coefficients of rhein were decreased with the increase of p H,and were 0.83 and 0.54 in phosphate buffer solution at p H 6.8 and 7.4,respectively.Conclusion Rhein is almost not soluble in water. With the raise of p H,the solubility is increased but the oil-water partition coefficient is decreased.
Objective To determine the solubility of rhein in different vehicles and its partition coefficients in the noctanol-water system for designing new formulations. Methods High performance liquid chromatography( HPLC) method was established to determine the concentration of rhein in water,different p H solutions and different solvents; the partition coefficients for the n-octanol-buffer solution systems were determined by shaking flask method. Results The equilibrium solubility of Rhein was 3.89 μg·m L-1 and the lg P was 2.79 in water at 37 ℃. The solubility of rhein was increased with the raise of p H,which could reach 362.20 and 431.65 μg·m L-1 in phosphate buffer solution at p H 6.8 and 7.4,respectively.Solubility of rhein in the semi polar solvent was relatively good,which can up to 2 971.74 μg·m L-1 in PEG400.The oil-water partition coefficients of rhein were decreased with the increase of p H,and were 0.83 and 0.54 in phosphate buffer solution at p H 6.8 and 7.4,respectively.Conclusion Rhein is almost not soluble in water. With the raise of p H,the solubility is increased but the oil-water partition coefficient is decreased.
引文
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[8]顾杰,李嬛,秦昆明,等.HPLC法测定甘草素的平衡溶解度和表观油水分配系数[J].药物分析杂志,2013,33(8):1293-1297.
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[2]YU L,YAO G,MA W.Rhein:a novel potential antitumor drug[J].Chin Pharm Sci,2016,25(5):321-328.
[3]尚小广,李颖,徐陆忠,等.大黄酸聚乳酸纳米粒的制备及大鼠体内药动学研究[J].中国药学杂志,2012,47(7):524-528.
[4]王亚乐,贾晓斌,陈彦,等.淫羊藿苷平衡溶解度和表观油水分配系数的测定[J].中华中医药杂志,2008,23(9):777-779.
[5]米楠,苏慕君,臧可昕.阿齐沙坦油水分配系数的测定[J].药学评价研究,2013,36(6):452-454.
[6]戚志华,郭淑云,唐秀玲,等.反相高效液相色谱法测定根皮苷平衡溶解度与油水分配系数[J].医药导报,2015,34(10):1329-1332.
[7]封玲,丁美红,沈勤,等.大黄酸神阙穴给药经皮渗透性的影响因素研究与初步机制探讨[J].中国中药杂志,2016,41(8):1546-1552.
[8]顾杰,李嬛,秦昆明,等.HPLC法测定甘草素的平衡溶解度和表观油水分配系数[J].药物分析杂志,2013,33(8):1293-1297.
[9]韩刚,王传胜,索炜,等.大黄酸固体分散体的制备[J].中国医院药学杂志,2011,31(13):1090-1093.