Position: Home > Articles > Determination of equilibrium solubility, apparent oil-water partition coefficient and dissociation constant for diflunisal
Journal of Traditional Chinese Veterinary Medicine
2023,42
(4)
61-65
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
作 者：
温莉珍;肖婷;何琳;刘蔚
单 位：
湖南冰溪生物科技有限公司;广州市第11人民医院;广东药科大学
关键词：
二氟尼柳;平衡溶解度;表观油水分配系数;解离常数
摘 要：
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（pK_a），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0.034 47 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0.055 04 mg/mL、0.225 30 mg/mL、0.555 60 mg/mL、1.520 00 mg/mL、2.558 00 mg/mL、2.671 00 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pK_a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。
译 名：
Determination of equilibrium solubility, apparent oil-water partition coefficient and dissociation constant for diflunisal
作 者：
WEN Lizhen;XIAO Ting;HE Lin;LIU Wei;Guangzhou Eleventh People's Hospital;Guangdong Pharmaceutical University;Hunan Bingxi Biological Technology Co., Ltd.;
关键词：
diflunisal;;equilibrium solubility;;apparent oil-water partition coefficient;;dissociation constant
摘 要：
To determine the equilibrium solubility(S), apparent oil-water partition coefficient P_(app)and dissociation constant(pK_a) 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 p H 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 0.034 47 mg/mL, and the apparent oil/water distribution coefficient lg P_(app)was 1.34. The equilibrium solubility of diflunisal in p H value 4.0, 5.0, 6.0, 7.0, 8.0 and9.0 were 0.055 04 mg/mL, 0.225 30 mg/mL, 0.555 60 mg/mL, 1.520 00 mg/mL, 2.558 00 mg/mL and 2.671 00 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 class Ⅱ drug in Biopharmaceutics Classification System(BCS).
