甘草酸对盐酸小檗碱溶解度和油水分配系数的影响

Effects of Glycyrrhizic Acid on Solubility of Berberine Hydrochloride and Oil-water Distribution Coefficient

目的:测定甘草酸对盐酸小檗碱平衡溶解度与油水分配系数的影响,为相关制剂研究提供参考。方法:采用摇瓶法-高效液相色谱法测定不同浓度甘草酸对盐酸小檗碱在水中溶解度的影响;测定甘草酸对盐酸小檗碱在正辛醇-水中的浓度并计算油水分配系数。结果:甘草酸浓度为10 mmol·L^(-1)时使得盐酸小檗碱在水中的溶解度和油水分配系数分别下降了2.3、10倍左右。在pH=6.8和pH=7.4介质中,甘草酸的存在使得小檗碱的P_(O/W)分别提高了11.23和2.48倍。结论:甘草酸的存在改变了盐酸小檗碱的溶解度和油水分配系数,可能会影响药物的体内行为和口服给药后的胃肠道吸收情况。

Objective:Determination of the equilibrium solubility of glycyrrhizic acid to berberine hydrochloride and oil-water partition coefficient,which laid the foundation for further study of the related preparations.Methods:The effects of different concentrations of glycyrrhizic acid on the solubility of berberine hydrochloride in water were determined by shaking flask method-high performance liquid chromatography.The concentration of glycyrrhizic acid in octanol-water was determined and the oil-water partition coefficient was calculated.Results:The solubility of berberine hydrochloride in water and the oil-water partition coefficient decreased by 2.3 and 10 times,when the concentration of glycyrrhizic acid was 10mmol·L-1.In the medium of pH 6.8 and pH 7.4,the presence of glycyrrhizic acid increased the Po/w of berberine by 11.23 and 2.48 times higer than that of the pure drugs respectively.Conclusion :The presence of glycyrrhizic acid changes the solubility and oil-water partition coefficient of berberine hydrochloride which may affect the in vivo behavior of the drug and the absorption of gastrointestinal tract after oral administration.