pH值对右旋布洛芬体外透皮性能的影响研究

Effect of pH Value on in Vitro Percutaneous Permeability for Dextral Ibuprofen

目的:研究pH值对右旋布洛芬(DI)体外透皮性能的影响,为其透皮给药制剂的开发提供实验依据。方法:建立DI的高效液相色谱分析方法,测定其在水和不同pH的磷酸盐缓冲液(PBS)中的平衡溶解度;用摇瓶法测定DI的正辛醇溶液在正辛醇饱和蒸馏水与不同pH的PBS中的表观油水分配系数;以稳态渗透速率(Js)和渗透系数(Ps)为评价指标,检测不同pH的PBS对DI体外透皮性能的影响。结果:32℃时,DI在水中难溶;在pH7.4的PBS中平衡溶解度、Js、Ps均最大,表观油水分配系数极小,分别为5421.6μg·mL-1、339.97μg·cm-2·h-1、0.063cm·h-1、0.17。结论:pH值对DI体外透皮性能有很大影响,pH7.4时DI有较高的溶解度、脂溶性及较理想的皮肤通透性。

OBJECTIVE： To study the effect of pH value on in-vitro percutaneous permeability of dextral ibuprofen （DI） and to provide experimental basis for the development of percutaneous agent. METHODS： HPLC method was established to determine the equilibrium solubility of DI in water and phosphate buffer solution （PBS） with different pH values. Shaking-flask method was used to measure the apparent oil-water distribution coefficient of DI in the n-octyl alcohol saturated water or PBS with different pH values. The effect of PBS with different pH values on in-vitro percutaneous permeability of DI was evaluated using the steady-state permeation rate （Js） and permeation coefficient （Ps） as index. RESULTS： At 32 ℃, DI was hardly soluble in water; the equilibrium solubility, J,, Ps of DI in PBS with pH 7.4 were the highest while apparent oil-water distribution coefficient was close to minimum value. They were 5 421.6 μg·mL-1, 339.97 μg·cm2-h-1, 0.063 cm·h-1, 0.17, respectively. CONCLUSION： The in-vitro percutaneous permeability of DI is greatly influenced by the pH of media. Adjusting pH to 7.4, higher solubility and liposolubility of dru~ are maintained as well as Dercutaneous t^ermeabilitv.