【摘要】 采用非对数电位滴定法对阿折地平多晶型(和晶型)的解离常数进行测定,以丙酮和水不同体积比的溶液为介质配制不同浓度的药物溶液,用盐酸溶液滴定,经逐步计算,外推到丙酮为0时得纯水中型和型的解离常数p分别为7.893 3和8.322 2,与采用ACD/pKa DB软件计算得出的理论值相近.采用摇瓶法测得两晶型在1∶1的正辛醇0.1 mmol L1盐酸溶液中的油水分配系数logP分别为0.505 4和0.495 7.多晶型虽然拥有同一分子结构式,但在分子构象上存在差异,影响其在水溶液中的解离行为,导致解离常数存在差异;阿折地平多晶型的脂溶性好,有利于跨膜转运.更多还原

【Abstract】 The dissociation constants of azelnidipine polymorphs €%Z and €%[ were determined by nonlogarithmic potentiotitration method.Different acetone/water volume ratio mixtures were used to prepare different concentration of azelnidipine solutions,which were titrated by hydrochloric acid standard solution.The dissociation constants of azelnidipine polymorphs €%Z and €%[ were calculated by extrapolating to the point of pure water;the values were 7.893 3 and 8.322 2,respectively,which were consistent with the theory values calculated by the soft of ACD/pKa DB.The oil-water partition coefficients logP of polymorphs €%Z and €%[ in n-octyl alcohol 0.1 mmolL solution were determined by shake-flask method;the values were 0.505 4 and 0.495 7,respectively.Although,polymorphs have the same chemical structure,the difference in molecular conformation could result in different dissociation behaviors and dissociation constants.The polymorphs of azelnidipine were liposoluble,which favored the transmembrane transport.更多还原