丹参提取物平衡溶解度及表观油水分配系数的测定

Determination of Equilibrium Solubility and Apparent Oil-Water Distribution Coefficient of Danshen Extract

目的 测定丹参提取物中“水-脂”二元组分指标成分在不同溶剂中的平衡溶解度及不同pH下的表观油水分配系数,探索丹参提取物的溶解性能。方法 应用超高效液相色谱法(UPLC)结合质量权重系数法表征丹参提取物中迷迭香酸、紫草酸、丹酚酸B、丹酚酸A、隐丹参酮及丹参酮ⅡA 6个指标成分在不同极性及pH值溶液中的整体溶解度和在饱和正辛醇-水系统中的整体油水分配系数。结果 37℃时提取物在水、甲醇、乙醇、乙腈、正丁醇、丙酮、三氯甲烷、乙酸乙酯八种溶剂中整体溶解性介于0.62~11.58 mg·mL-1之间,在水中的平衡溶解度较大;在缓冲液中平衡溶解度呈先增大后减小,最后趋于稳定的趋势;饱和正辛醇-水系统中的整体油水分配系数Kapp介于-1.12~-0.16之间,pH为4.97时lgP达到最大。结论 丹参提取物溶解性与渗透性均差,在剂型设计时可考虑在处方中加入适量醇类提高溶解度,调节pH值、利用促渗方法等促进药物经皮吸收。

Objective To determine the equilibrium solubility of the“water lipid”binary component index components in different solvents and the apparent oil-water distribution coefficient at different pH values in Danshen extract,and to explore the solubility performance of Danshen extract.Methods Ultra high performance liquid chromatography(UPLC)combined with mass weighting coefficient method was used to characterize the overall solubility of six indicator components,including rosmarinic acid,purpuric acid,salvianolic acid B,salvianolic acid A,cryptotanshinone,and salvianone IIA,in solutions of different polarities and pH values,as well as the overall oil-water distribution coefficient in a saturated n-octanol water system in Danshen extract.Results At 37℃,the overall solubility of the extract in eight solvents including water,methanol,ethanol,acetonitrile,n-butanol,acetone,trichloromethane,and ethyl acetate ranged from 0.62 to 11.58 mg·mL-1,and the equilibrium solubility in water was relatively high;The equilibrium solubility in the buffer solution shows a trend of first increasing,then decreasing,and finally stabilizing;The overall oil-water distribution coefficient Kapp in the saturated n-octanol water system ranges from-1.12 to-0.16,and the lgP reaches its maximum at pH 4.97.Conclusion The solubility and permeability of Danshen extract are both poor.When designing the dosage form,it is possible to consider adding an appropriate amount of alcohols to the prescription to improve solubility,adjust pH value,and use permeation promoting methods to promote drug transdermal absorption.