维他昔布表观油水分配系数和平衡溶解度的测定

Determination of Apparent Oil-water Partition Coefficient and Equilibrium Solubility of Vitacoxib

目的:研究维他昔布在不同介质溶液中的表观油水分配系数和平衡溶解度。方法:采用高效液相色谱法和饱和溶解度法测定维他西布37℃时在0.1mol/L盐酸,pH2.0、5.8、6.8、7.4的磷酸盐缓冲液(PBS液),水,0.5%十二烷基硫酸钠和0.5%聚山梨酯80的溶液中的平衡溶解度;通过维他昔布分配平衡后在油相(正辛醇)和水相的浓度比,计算表观油水分配系数的lg值(lgP)。结果:维他昔布在上述溶液中的平衡溶解度分别为6.62、8.66、6.65、14.41、27.38、55.65、96.17、18.37μg/ml,lgP分别为0.45、0.61、0.43、0.40、0.44、0.47、0.35、0.21。结论:维他昔布是亲脂性药物,在水中溶解度小,在0.5%十二烷基硫酸钠溶液中的溶解度最大,推测其在体内吸收较差。

OBJECTIVE： To study the equilibrium solubility and the apparent oil-water partition coefficient of vitacoxib in different medium. METHODS： The equilibrium solubility of vitacoxib in 0.1 mol/L hydrochloric acid, PBS solution （pH 2.0, 5.8, 6.8, 7.4）, water, 0.5% sodium dodecyl sulfate solution and 0.5% Polysorbate 80 solution at 37 ℃ were determined by HPLC and saturation method. The apparent oil-water partition coefficient was calculated with concentration ratio of vitacoxib in oil phase （n-octanol） and water phase after partition equilibrium. RESULTS： The equilibrium solubility of vitacoxib were 6.62, 8.66, 6.65, 14.41, 27.38, 55.65, 96.17 and 18.37 μg/ml; and the lgP of apparent oil-water partition coefficient of vitacoxib were 0.45, 0.61, 0.43, 0.40, 0.44, 0.47, 0.35 and 0.21, respectively. CONCLUSIONS： Vitacoxib is a lipophilic drug, and the solubility of vitacoxib in water is poor. The solubility of vitacoxib in 0.5% sodium dodecyl sulfate solution is the largest, which indicates that in vivo absorption of vitacoxib is not good.