非布索坦平衡溶解度表观油水分配系数及解离常数的测定张琪.docVIP

Chinese Journal of New Drugs 2013，22（1） ·实验研究· 非布索坦平衡溶解度、表观油水分配系数及解离常数的测定 张 琪，龚耘，劳嘉泳，张怡，刘中秋，蔡 （南方医科大学药学院，广州510515） 铮 ［摘要］目的：测定非布索坦的平衡溶解度、表观油水分配系数及解离常数。方法：采用超高效液相色 并分别通过平衡溶解谱法测定非布索坦在37? 下不同pH 值缓冲液中的平衡溶解度及表观油水分配系数， 度法及紫外吸光度法测定其解离常数。结果：非布索坦的平衡溶解度随缓冲液的pH 值升高而增大，而表观 ·L －1，油水分配系数则相应减小，当pH 为7．0时，平衡溶解度为246．4mg 表观油水分配系数为15．49；平衡溶解度法与紫外吸光度法测得的非布索坦的解离常数十分接近，分别为4．08与4．07。结论：非布索坦的溶 解度较小，在酸性条件下几乎不溶，中性条件下极微溶解，碱性条件下微溶，不适合制备静注制剂，但由于其油水分配系数较高，具有较强的跨膜能力，可采用口服途径给药。 ［关键词］非布索坦；平衡溶解度；表观油水分配系数；解离常数 ［中图分类号］R913 ［文献标志码］A ［文章编号］1003－3734（2013）01－0103－04 Determination of equilibrium solubility ，apparent oil /waterpartition coefficient and dissociation constant of febuxostat ZHANG Qi ，GONG Yun ，LAO Jia-yong ，ZHANG Yi ，LIU Zhong-qiu ，CAI Zheng （School of Pharmaceutical Sciences ，Southern Medical University ，Guangzhou 510515，China ） ［Abstract ］Objective ：To determine equilibrium solubility （C s ），apparent oil /waterpartition coefficients （P app ）and dissociation constant （p K a ）of febuxostat．Methods ：Ultra performance liquid chromatography method was established to measure equilibrium solubility and log P app of febuxostat at 37? in buffer solutions with various pH values．The p K a was determined by equilibrium solubility method and UV spectrophotometry ，respectively．Re-sults ：With the rise of pH value ，the C s of febuxostat increased correspondingly ，and apparent oil /waterpartition coefficients decreased inversely．When the pH value was 7．0，C s was 246．4mg ·L －1and log P app was 1．19．The p K a values measured by equilibrium solubility method and UV spectrophotometry were 4．08and 4．07，respective-ly．Conclusion ：Febuxostat is insoluble in acidic condition ，very slight soluble in neutral condition ，and slight sol-uble in alkaline condition ；thus ，it is unsuitable for intravenous injection because of the poor water solubility．How-ever ，oral administration is recommended due to its proper lipophilicity and high permeability． ［Key words ］febuxostat ；equilibrium solubility ；apparent oil /waterpartition