吲哚美辛水凝胶贴剂小鼠体外透皮性能研究

目的：通过研究不同促透剂对吲哚关辛水凝胶贴剂透皮性能的影响，遴选在特定栽药剂量时具有最佳促透效果的促透剂，并与市售贴剂进行比较，对吲哚美辛水凝胶贴剂的体外透皮性能进行评价。方法：采用改良Franz透皮扩散池，以离体小鼠背部皮肤为透皮屏障，在最佳载药量选用不同浓度的氮酮、油酸、丙二醇以及三者组成的二元或三元组合为促透剂，在规定时间点测定吲哚美辛的累积透过百分率以及单位面积累积透过量。结果：与空白对照组相比，当氮酮与油酸单独应用时，二者均没有明显的促透作用；当选用二元促透剂联合应用时，油酸与丙二醇联用能够明显促进吲哚美辛的经皮渗透（P〈0．05）；当选用三元促透剂时促透效果更好，单位面积累积透过量最高可达234．4μg·cm^-2，24h内药物累积透过百分率明显高于市售贴剂。结论：氮酮、油酸、丙二醇三者联合应用可作为吲哚关辛贴剂的理想促透剂。吲哚关辛水凝胶贴剂是具有应用价值的新型经皮控释制剂。

Study on Transdermal Permeation of Indomethacin Hydrogel Patch in Vitro

Objective： To screen the optimal penetration enhancer at certain drug loading for indomethacin hydrogel patch, to in- vestigate the effects of several penetration enhancers on transdermal permeation of indomethacin, and to evaluate transdermal permeation of indomethacin hydrogel patch by comparing it with the commercial patch. Methods： Franz diffusion cell was adopted as the apparatus for transdermal permeation test and excised mouse back skin as transdermal permeation barrier. The percentage of cumulative permeation and accumulated absorption ofindomethacin per unit area were determined at a certain time with the optimal drug loading, with AZ, OA, PG, and their binary and ternary were used as penetration enhancers. Results： Compared with that in the blank group, AZ and OA showed no significant enhancing effect on the accumulated absorption per unit area of indomethacin when they were used separately. Of the binary penetration enhancers, OA ＋ PG enhanced transdermal permeation of indomethacin distinctly （P〈0.05）. The ternary penetration enhancer had the largest accumulated absorption of 234.4 μg. cm^-2 per unit area. Indomethacin hydrogel patch had distinctly higher percentage of cumulative permeation in 24 h than the commercial patch. Conclusion： The ternary penetration enhancer can be used as the optimal penetration enhancer for indomethaein hydrogel patch. And the indomethacin hydrogel patch is a new transdermal controlled-re- lease formulation with application value.