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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,5μm)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 for providing experimental basis for drug evaluation and new formulation design and development. Methods The equilibrium solubility of diclofenac sodium in different media was determined by reversed-phase high-performance liquid chromatography (RP-HPLC). The chromatographic column was Diamonsil C18 (150 mm × 4.6 mm, 5 μm) 1) as mobile phase, the volume flow rate was 0.8 mL / min, the detection wavelength was 276 nm, and the column temperature was 32 ℃. The apparent oil-water partition coefficients of diclofenac sodium in n-octanol-water / . Results The equilibrium solubility of diclofenac sodium in distilled water and normal saline at 32 ℃ was 18.2 and 5.52 mg / mL respectively. The equilibrium solubilities of diclofenac sodium in isopropyl myristate (IPM) and ethyl oleate were 0.637 and 1.97 mg / mL. The apparent oil-water partition coefficient in n-octanol / water system was 1.41 (lgP = 0.15). The equilibrium solubility increased with the increase of pH in pH 5.0-7.4 buffer solution. Apparent oil-water partitioning The coefficient decreased with the increase of pH value. Conclusion pH had a significant effect on the equilibrium solubility of diclofenac sodium and apparent oil-water partition coefficients.