二氟尼柳平衡溶解度、表观油水分配系数及解离常数的测定

Determination of equilibrium solubility,apparent oil-water partition coefficient and dissociation constant for diflunisal

考察二氟尼柳在25℃、不同pH值条件下的平衡溶解度(S)、表观油水分配系数P_(app)及解离常数(pKa),为二氟尼柳新剂型的研究提供依据。采用紫外分光光度法测定二氟尼柳在水及pH值为4~9的磷酸盐缓冲溶液中的平衡溶解度;采用摇瓶法测定二氟尼柳在正辛醇-水/pH值为4~9的磷酸盐缓冲溶液中的表观油水分配系数;采用紫外分光光度法测定二氟尼柳的解离常数。结果显示,25℃时,二氟尼柳在水中的S值为0.03447 mg/mL,lg P_(app)为1.34;在pH值为4.0、5.0、6.0、7.0、8.0、9.0的磷酸盐缓冲液中,S值分别为0.05504 mg/mL、0.22530 mg/mL、0.55560 mg/mL、1.52000 mg/mL、2.55800 mg/mL、2.67100 mg/mL;相应条件下的lg P_(app)为1.31、1.36、0.93、0.40、0.01、-0.03;解离常数pKa值为5.53。二氟尼柳的平衡溶解度和表观油水分配系数与溶液的pH值相关,随着溶液pH值的升高,溶解度增大,油水分配系数减小,属于生物药剂学分类系统(BCS)Ⅱ类药物。

To determine the equilibrium solubility(S),apparent oil-water partition coefficient P_(app)and dissociation constant(pKa)of diflunisal with different pH value at 25℃,and provide a theoretical basis for its formulation study.The equilibrium solubility of diflunisal in water and different pH media(4-9)were determined by ultraviolet spectrophotometry,and the apparent oil/water distribution coefficient of diflunisal in n-octanol-water/buffering system was determined by shaking flask method.The dissociation constant of diflunisal was determined by ultraviolet spectrophotometry.The results showed that at 25℃,the equilibrium solubility of diflunisal in water was 0.03447 mg/mL,and the apparent oil/water distribution coefficient lgP_(app)was 1.34.The equilibrium solubility of diflunisal in pH value 4.0,5.0,6.0,7.0,8.0 and 9.0 were 0.05504 mg/mL,0.22530 mg/mL,0.55560 mg/mL,1.52000 mg/mL,2.55800 mg/mL and 2.67100 mg/mL,and the apparent oil-water distribution coefficient was 1.31,1.36,0.93,0.40,0.01 and-0.03,respectively.The dissociation constant of diflunisal was 5.53.The pH value can affect the equilibrium solubility and oil-water distribution coefficient of diflunisal,good solubility in water and poor oil-water distribution coefficient can be obtained with increasing pH value.Diflunisal can be categorized as classⅡdrug in Biopharmaceutics Classification System(BCS).