pH值对瑞格列奈平衡溶解度及油水分配系数的影响

Effect of pH Value on Equilibrium Solubility and Oil Water Partition Coefficient of Repaglinide

目的测定瑞格列奈在不同pH溶液中的平衡溶解度及其在正辛醇-水系统中的油水分配系数,为瑞格列奈动力学性质、新剂型设计和生物药剂学分类提供依据。方法采用摇瓶-高效液相色谱法分别测定瑞格列奈在不同pH溶液中的平衡溶解度和正辛醇-水/缓冲液体系中的油水分配系数。结果在37℃下,瑞格列奈在pH为1.0、2.0、3.0、4.0、5.0、6.8缓冲液和水中,平衡溶解度分别为6.596、0.810、0.082、0.014、0.009、0.061和0.015 mg·mL^(-1),平均油水分配系数分别为0.9、1.7、2.7、3.4、3.6、2.9和2.6。结论瑞格列奈为低溶解性,脂溶性好的药物,而且其平衡溶解度和油水分配系数与pH密切相关,本研究可以佐证其属于生物药剂学(BCS)分类系统中的Ⅱ类药物。

OBJECTIVE To determine the equilibrium solubility of repaglinide in solution with different pH conditions and its oil water partition coefficient in n-octanol-water system,so as to provide the basis for the kinetic properties of repaglinide,the design of new dosage forms and the classification of Biological Pharmaceutics(BCS).METHODS The equilibrium solubility of repaglinide in different pH solutions and the partition coefficient of oil and water in n-octanol-water/buffer system were determined by shaking flask HPLC.RESULTS At 37℃,the equilibrium solubility of repaglinide was 6.596,0.810,0.082,0.014,0.009,0.061 and 0.015 mg·mL-1 in pH 1.0,2.0,3.0,4.0,5.0,6.8 buffer solution and water,and the average oil water partition coefficients were 0.9,1.7,2.7,3.4,3.6,2.9 and 2.6,respectively.CONCLUSION Repaglinide is a drug with low solubility and good fat solubility,and its equilibrium solubility and oil water partition coefficient are closely related to pH.This study can prove that it belongs to the classⅡdrug in Biological Pharmaceutics(BCS)classification system.