目的:测定盐酸奈必洛尔的平衡溶解度和表观油水分配系数,为药物新剂型的研究与开发提供试验基础.方法:采用高效液相色谱法测定盐酸奈必洛尔溶液的含量,运用饱和溶液法测定盐酸奈必洛尔在纯水、0.1 mol·L-1 盐酸溶液及不同pH磷酸盐缓冲液(pH2.0,pH6.8,pH7.4,pH8.0)中的平衡溶解度;通过摇瓶法测定其在正辛醇-水/缓冲液体系中的表观油水分配系数.结果:(37±0.5)℃下,盐酸奈必洛尔在纯水和0.1 mol·L-1 盐酸的平衡溶解度分别为722.53 μg·ml-1和56.07 μg·ml-1,在正辛醇-水/盐酸体系中表观油水分配系数(Log P)分别为1.17和1.32.在pH2.0~7.4的磷酸盐缓冲液中,盐酸奈必洛尔的平衡溶解度和表观油水分配系数随pH升高,分别呈现出降低和增加的趋势;而当pH从7.4增加至8.0时,平衡溶解度增加,表观油水分配系数降低.结论:本文建立的含量测定方法简单可靠,盐酸奈必洛尔水溶性差,其平衡溶解度和表观油水分配系数呈现出pH依赖性.%Objective:To determine the equilibrium solubility and the apparent oil/water partition coefficient of nebivolol hydrochloride to provide experimental basis for the development of new preparations.Methods:The concentration of nebivolol hydrochloride was determined by an HPLC method,and a saturated solution method and a shake-flask method were respectively applied to determine the equilibrium solubility and the apparent oil/water partition coefficient of nebivolol hydrochloride in water,0.1 mol·L-1 HCl solution and phosphate buffer solution with different pH values(pH2.0,pH6.8,pH7.4 and pH8.0).Results:At (37±0.5)℃,the equilibrium solubility of nebivolol hydrochloride in water and in 0.1 mol·L-1 HCl solution was 722.53 μg·ml-1and 56.07μg·ml-1,respectively.The apparent oil/water partition coefficient (Log P) of nebivolol hydrochloride was 1.17 and 1.32,respectively.Within the pH range of 2.0-7.4,with the increase of pH value, the equilibrium solubility and the Log P decreased and increased,respectively,while pH value increased from 7.4 to 8.0,the equilibrium solubility of nebivolol hydrochloride increased and Log P decreased.Conclusion:The method is accurate and reliable.Nebivolol hydrochloride has poor water solubility,and the equilibrium solubility and the Log P are both influenced by pH values.
展开▼
