阿苯达唑的平衡溶解度和表观油水分配系数的测定

Determination of Equilibrium Solubility of Albendazole and Its Apparent Oil-Water Partition Coefficient

目的:测定阿苯达唑的平衡溶解度和表观油水分配系数。方法:采用高效液相色谱法和饱和溶解度法测定阿苯达唑在37℃下,在水、7种常用不同极性强度有机溶剂(甲醇、乙醇等)、有机酸(油酸、冰醋酸、乳酸、甲酸)、p H 1.2盐酸、不同p H(2.0~7.8)磷酸盐缓冲液(PBS)和质量浓度分别为10、50、100 mg/ml的6种常用表面活性剂(聚山梨酯80、泊洛沙姆等)中的平衡溶解度;通过阿苯达唑分配平衡后在油相(正辛醇)和水相(水及不同p H的PBS)的浓度比,计算表观油水分配系数(P)。结果:阿苯达唑在水中的平衡溶解度为(0.26±0.02)μg/ml,lg P为3.66±0.01;在常用有机溶剂和有机酸中的平衡溶解度均较在水中高,有机溶剂的极性强度越大,有机酸酸性越弱,其对阿苯达唑的增溶能力越小;在p H 1.2~2.5介质中的平衡溶解度较在p H 5.0~7.8介质中高;表面活性剂对阿苯达唑的增溶能力与其种类有关,且表面活性剂质量浓度越大,增溶能力越强;在p H 1.2~2.0条件下lg P小于1.6,在p H 5.0~7.8条件下lg P变化不大[(3.71±0.26)^(3.68±0.26)]。结论:阿苯达唑难溶于水,其平衡溶解度与有机溶剂极性强度呈负相关,与有机酸酸性呈正相关,与表面活性剂质量浓度呈正相关;在强酸性环境中,阿苯达唑水溶性较强、脂溶性弱,在弱酸、弱碱和中性环境中脂溶性较强、水溶性弱。

OBJECTIVE：To determine the equilibrium solubility of albendazole（ABZ）and its apparent oil-water partition coefficient.METHODS：The equilibrium solubility of ABZ in various solutions was determined at 37 ℃ by HPLC and saturation solubility method,including water,7 kinds of common organic solvents with different polarities（methanol,ethanol,etc.）,organic acid（oleic acid,glacial acetic acid,lactic acid,formic acid）,hydrochloric acid of p H 1.2,phosphate buffer solution（PBS）of different p Hs（2.0-7.8）and 6 kinds of common surfactants with mass concentrations of 10,50 and 100 mg/ml（polysorbate 80,poloxamer,etc.）.The apparent oil-water partition coefficient（P）was calculated with the concentration ratio of ABZ in oil phase（N-octyl alcohol）and water phase（water and PBS of different p Hs）after partition equilibrium.RESULTS：The equilibrium solubility of ABZ reached（0.26±0.02）μg/ml in water,with the lg P of 3.66±0.01.The equilibrium solubility of ABZ in common organic solvents and organic acids was higher than in water.The higher the polarity of the organic solvent was and the weaker of organic acid was,the weaker of its ability to solubilize ABZ would be.The equilibrium solubility of ABZ was higher in the medium of p H1.2-2.5 than in that of p H 5.0-7.8.The ability of the surfactant to solubilize ABZ was related to its type,and the higher of the mass concentration of the surfactant was,the stronger of its ability to solubilize ABZ became.lg P was less than 1.6 at p H 1.2-2.0 and changed little at p H 5.0-7.8 [（3.71 ± 0.26）-（3.68 ± 0.26）].CONCLUSIONS：ABZ is insoluble in water.Its equilibrium solubility demonstrates a negative correlation with the polarity of the organic solvent and a positive correlation with the acidity of the organic acid and with the mass concentration of the surfactant.It has higher water solubility and lower lipid solubility in a strong acidic environment,and higher lipid solubility and weaker water solubility in weak acidic,weak basic and neutral environments.