水杨酸微乳的制备及其体外透皮吸收研究

Preparation of Salicylic Acid Microemulsion and Its in vitro Percutaneous Permeation

目的:制备水杨酸微乳并考察其对离体小鼠皮肤经皮吸收的影响。方法:以聚山梨酯80为乳化剂、丙二醇为助乳化剂、油酸乙酯为油相,通过伪三元相图确定微乳的处方。采用激光粒度分析仪测定微乳的粒径分布;采用紫外分光光度法测定水杨酸含量;采用Franz扩散池法比较所制备的水杨酸微乳与市售水杨酸软膏的体外透皮速率。结果:水杨酸微乳的处方为5%水杨酸、6.8%油酸乙酯、32.4%混合乳化剂(聚山梨酯80-丙二醇之比为4∶1)。所制得的水杨酸微乳为O/W型微乳,粒径为(70.35±17.78)nm;其与市售水杨酸软膏的稳定渗透速率分别为(573.72±8.94)、(310.52±7.11)μg/(cm2·h),渗透系数分别为(1.588±0.019)、(0.430±0.001 2)cm/h,前者为后者的3.69倍;水杨酸微乳的透皮吸收行为符合零级动力学释放规律。结论:所制水杨酸微乳可促进水杨酸的透皮吸收,为制备胃肠道刺激性小、生物利用度高的水杨酸新剂型提供一定的理论依据。

OBJECTIVE： To prepare Salicylic acid microemulsion, and to investigate its in vitro percutaneous permeation in isolated mice skin. METHODS： The microemulsion was prepared using tween-80 as emulsifiers, propylene glycol as assistant emulsifiers and ethyl oleate as oil phase. The formulation was optimized by pseudo-ternary phase diagram, and the distribution of parti- cle size was determined by laser particle analyzer. The content of salicylic acid was determined by UV spectrophotometry. The in vitro percutaneous rates of prepared Salicylic acid microemulsion and commercially available Salicylic acid cream were determined by Franz diffusion cell. RESULTS： The formula of Salicylic acid microemulsion was as follows： 5% salicylic acid, 6.8% ethyl oleate, 32.4% mixture surfactant （tween-80/propylene glycol ratio of 4： 1）. The prepared Salicylic acid microemulsion was O/W micro- emulsion with particle size of （70.35 ± 17.78） nm. Steady permeation rates of prepared microemulsion and commercially available cream were （573.72 ± 8.94） gg/（cm2.h） and （310.52 ± 7.11） gg/（cm2.h）, respectively; the permeation coefficient of them were （1.588 ± 0.019） cm/h and （0.430 ± 0.001 2） era/h, and the former was 3.69 times of the latter. The percutaneous permeation behavior of Salicylic acid mieroemulsion was in line with zero-order kinetic release rules. CONCLUSIONS： Prepared Salicylic acid microemulsion can improve the percutaneous permeation of salicylic acid, and to provide theoretic basis for the preparation of new dosage form with less gastrointestinal irritation and high bioavailability.