目的 測定雙氯芬酸鈉平衡溶解度及表觀油水分配系數(shù)，為藥物評價、新劑型設計與開發(fā)提供試驗依據。方法 采用反相高效液相色譜法（RP-HPLC）測定雙氯芬酸鈉在不同介質中的平衡溶解度，使用Diamonsil C₁₈（150 mm×4.6 mm，5 μm）色譜柱，甲醇-水-磷酸（80∶19∶1）為流動相，體積流量為0.8 mL/min，檢測波長為276 nm，柱溫為32 ℃；采用搖瓶法測定雙氯芬酸鈉在正辛醇-水/緩沖液體系中的表觀油水分配系數(shù)。結果 32 ℃時，雙氯芬酸鈉在蒸餾水和生理鹽水中的平衡溶解度分別為18.2、5.52 mg/mL；在肉豆蔻酸異丙酯（IPM）、油酸乙酯中的平衡溶解度分別為0.637、1.97 mg/mL；在正辛醇/水體系中的表觀油水分配系數(shù)為1.41（lgP＝0.15）；在pH 5.0～7.4緩沖液中，其平衡溶解度隨pH值升高而增大，表觀油水分配系數(shù)隨pH值升高而降低；結論 pH對雙氯芬酸鈉的平衡溶解度和表觀油水分配系數(shù)有較大影響。

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.

山西省科技廳基礎研究項目（2012011007-5）；山西醫(yī)科大學青年基金項目（02200908）