川芎嗪平衡溶解度及油/水分配系数的研究

目的测定川芎嗪在不同pH值下的平衡溶解度和油水分配系数(P)。方法采用摇瓶法测定表观溶解度,通过药物分配平衡后在油相和水相中的浓度比,计算油水分配系数。结果川芎嗪在二氯甲烷、乙腈、乙酸乙酯等有机溶剂中溶解度较大,在聚乙二醇400中不溶。在蒸馏水中几乎不溶,随着pH值增大,川芎嗪的溶解度变小;川芎嗪正辛醇溶液质量浓度对川芎嗪油水分配系数无明显影响,pH值对川芎嗪油水分配系数有影响,随pH值增大川芎嗪油水分配系数增大。结论药物在水中的平衡溶解度及油水分配系数与介质的pH值有关,当pH>7.24时,川芎嗪的溶解度陡然下降;当pH>6.8时,药物在油相中分配较多,川芎嗪在正辛醇-水体系中的油水分配系数P=12.33。

Study on balance solubility and oil/water partition coefficient of tetramethylpyrazine

OBJECTIVE To determine the equilibrium solubility and apparent oil/water partition coefficient（P） of tetramethylpyrazine（TMPZ） in a series of solutions of different pH value.METHODS The apparent solubility was determined by shake-flask method.The oil/water partition was calculated with concentration ratio of TMPZ in n-octyl alcohol and water phase after partition equilibrium.RESULTS The solubility of TMPZ was large in organic solvents such as dichloromethane,acetonitrile,ethylacetate.And it was not dissolved in PEG400.TMPZ was almost insoluble in distilled water,with the pH increases,the solubility of TMPZ smaller;and the oil/water partition coefficient of TMP was not significant effected by the TMPZ concentration of n-octyl alcohol solution,but it increased with the increase of the pH value.CONCLUSION The equilibrium solubility and apparent oil/water partition coefficient of TMPZ were related to the pH value of the medium.The distribution of TMPZ in the oil phase was more when pH7.24,and the solubility of TMPZ dropped precipitously when pH6.8.The apparent oil/water partition coefficient of TMPZ in n-octyl alcohol-water system was 12.33.