氧化苦参碱的理化常数

目的测定氧化苦参碱的溶解度、解离常数(pKa)、油水分配系数(P)等理化常数,指导药物剂型的合理设计。方法按《中华人民共和国药典》中溶解度的测定方法测定氧化苦参碱在不同溶剂中的近似溶解度;采用电位滴定法、分光光度指示剂法测定氧化苦参碱的pKa值;采用摇瓶法测定氧化苦参碱在不同pH下的表观油水分配系数。结果氧化苦参碱在水、0.15 mol.L-1柠檬酸、0.15 mol.L-1碳酸钠溶液、甲醇、氯仿中溶解良好,在质量分数为20%的氢氧化钠溶液、石油醚和乙酸乙酯中溶解度都很低;电位滴定法、分光光度指示剂法测得的氧化苦参碱pKa分别为6.98、6.71;氧化苦参碱表观油水分配系数随着pH值的增加而增加,其真实油水分配系数为0.2。结论氧化苦参碱是一个亲水性很强的弱碱性药物。

Physicochemical constants of oxymatrine

Objective To study the drug physicochemical properties for rational formulation design.Methods The approximate solubilities in different aqueous media and organic solvents were determined according to the method in Chinese Pharmacopeia.The dissociation constant(pK_a)of oxymatrine was determined according to both potential titration and spectrophotometric indicator method.The apparent n-octanol-water partition coefficient(P_(O/W))of oxymatrine was measured by shake-flask method.Results The approximate solubilities of oxymatrine is high in distilled water,sodium carbonate solution((0.15 mol·L~(-1))),citric acid solution((0.15 mol·L~(-1))),methanol and chloroform,but it is low in sodium hydroxide solution(20%),petroleum ether and ethyl acetate.The pK_a values of oxymatrine determined by potential titration and spectrophotometric indicator method were 6.98 and 6.71 respectively.The true P_(O/W) of oxymatrine obtained at pH 10 was 0.2.Conclusions Oxyamtrine is a weak base with high hydrophilicity.