目的 测定双氯芬酸钠平衡溶解度及表观油水分配系数，为药物评价、新剂型设计与开发提供试验依据。方法 采用反相高效液相色谱法（RP-HPLC）测定双氯芬酸钠在不同介质中的平衡溶解度，使用Diamonsil C₁₈（150 mm×4.6 mm，5 μm）色谱柱，甲醇-水-磷酸（80∶19∶1）为流动相，体积流量为0.8 mL/min，检测波长为276 nm，柱温为32 ℃；采用摇瓶法测定双氯芬酸钠在正辛醇-水/缓冲液体系中的表观油水分配系数。结果 32 ℃时，双氯芬酸钠在蒸馏水和生理盐水中的平衡溶解度分别为18.2、5.52 mg/mL；在肉豆蔻酸异丙酯（IPM）、油酸乙酯中的平衡溶解度分别为0.637、1.97 mg/mL；在正辛醇/水体系中的表观油水分配系数为1.41（lgP＝0.15）；在pH 5.0～7.4缓冲液中，其平衡溶解度随pH值升高而增大，表观油水分配系数随pH值升高而降低；结论 pH对双氯芬酸钠的平衡溶解度和表观油水分配系数有较大影响。

Objective To determine the equilibrium solubility and apparent oil/water partition coefficient of diclofenac sodium, and to provide the experimental basis for the drug evaluation and the research and development of new dosage form design of diclofenac sodium. Methods RP-HPLC method was used to determine the concentration of diclofenac sodium in different media. A column of Diamonsil C₁₈ was used for separation column (150 mm × 4.6 mm, 5 μm). The mobile phase was consisted of methanol-water-K₃PO₄ (80:19:1). The flow rate was 0.8 mL/min. The detective wavelength was set at 276 nm, and the column temperature was 32 ℃. The apparent oil/water partition coefficients for the octanol-water/buffer solution systems of diclofenac sodium were determined by shaking flash method. Results The equilibrium solubility of diclofenac sodium in water and normal saline was 18.2 and 5.52 mg/mL at 32 ℃ respectively, and the equilibrium solubility of diclofenac sodium in isopropyl myristate (IPM) and ethyl acetate were 0.637 and 1.97 mg/mL respectively; The apparent partition coefficient of diclofenac sodium in the octanol-water solution system was 1.41 (lgP = 0.15); The equilibrium solubility and apparent partition coefficient of diclofenac sodium were increased and diminished respectively when pH value increased from 5.0 to 7.4 in various pH buffer solutions. Conclusion The equilibrium solubility and apparent oil/water partition coefficient of diclofenac sodium are greatly influenced by the pH value of media.

山西省科技厅基础研究项目（2012011007-5）；山西医科大学青年基金项目（02200908）