COMBINED EFFECT OF ULTRASOUND AND CHEMICAL ENHANCERS ON THE SKIN PERMEATION OF AMINOPYRINE

The combined effect of 150 kHz ultrasound with 111 mW/cm(2) intensity and chemical enhancers on the skin permeation of aminopyrine (AMP) was investigated using excised hairless rat skin. Monoterpenes (L-menthol , L-calvone and D-limonene), laurocapram (Azone(R)), glycerol monocapr ylate (Sefsol-318(R)), isopropyl myristate and ethanol were selected a s enhancers. Combined application of ultrasound and enhancers increase d the skin permeation rate (flux) of AMP compared with ultrasound or e nhancers alone. Better effects were obtained by the combination with m onoterpenes. The influence of detailed conditions of ultrasound and en hancer applications on the AMP flux was further investigated using L-m enthol. The enhancement effect by this combination was increased with an increase in ultrasonic application duration and L-menthol concentra tion, suggesting that these conditions might be used to achieve the co ntrolled drug delivery. A pretreatment experiment with ultrasound or L -menthol was carried out, and L-menthol content in the skin and the sk in permeation of deuterium oxide (D2O), used as a donor vehicle, were measured to understand the role of ultrasound in the combined effect. Application of ultrasound to the L-menthol-pretreated skin increased t he AMP flux, while the effect of L-menthol on ultrasonic-pretreated sk in was similar to that of L-menthol alone. The ultrasound increased th e L-menthol content in the skin as well as the skin permeation of D2O from a vehicle with L-menthol. These results suggested that simultaneo us application of ultrasound and enhancers is essential to obtain the pronounced effect. Ultrasound application also strongly assisted migra tion of L-menthol into skin, which increases the enhancing action on t he skin permeation for a drug.