Synergistic Effect of Mixed Cosurfactants on Transdermal Delivery of Indomethacin from O/W Microemulsion

t Since large amounts of oils, surfactants and penetration enhancers used in microemulsion systems might lead to seriously skin irritation, the percutaneous absorption and penetration of indomethacin（IMC, model drug） from O/W microemulsion were enhanced by simply changing the composition of cosurfactants. Pseudo-ternary phase dia- grams were constructed with mixed cosurfactants at different ratios. Hairless rat skin was used as a barrier for per- meation experiments. Four formulations were prepared with fixed oil, surfactant and different cosurfactant con- tent（4%, 20% and 20%, mass fraction）, and formulation F4 with menthol added was evaluated to compare the en- hancement effect of it with those of mixed cosurfactants. The O/W microemulsion region was the largest when the mass ratio of ethanol/transcutol was 1：1. However, the region changed slightly for the system with incorporated mixed cosurfactants propylene glycol/transcutol. The flux and skin retention of IMC from O/W microemulsion with mixed cosurfactants were much higher than that with single cosurfactant（P〈0.01）, while incorporation of menthol would only enhance the drug flux through the skin. To conclude, mixed cosufactants could affect the phase behavior and improve the percutaneous absorption and penetration of IMC. Based on this, it provided a promising solution to enhance drug release from microemulsions without raising potential skin damage.