Physicochemical properties study 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.