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

The combined effect of 800 kHz ultrasound with 2W/cm2 intensity and chemical enhancers on the skin permeation of caffeine was investigated using excised ear rabbit skin. Menthol, laurocapram (Azone®), isopropyl myristate and ethanol were selected as enhancers. Caffeine permeation was increased upon incorporation of all enhancers. The steady state fluxes were 05.69, 10.13, 22.42 and 25.06 µg/cm2 per h with enhancement factor equals 1.38, 2.458, 5.441 and 6.083 for 40% EtOH, 10% IPM, 3% AZ and 5% M, respectively. Combined application of ultrasound and enhancers increased the skin permeation rate (flux) of caffeine compared with ultrasound or enhancers alone. The enhancement factor equals 1.485, 4.514, 18.572, and 48.610 for 40% EOH, 10% IPM, 3% AZ and 5% M respectively. Better effects were obtained by the combination with 5%M. The influence of detailed conditions of ultrasound and enhancer applications on the caffeine flux was further investigated using 5% M. Caffeine fluxes were, 95.254, 115.368 and 200.06 µg/cm2 per h upon application of ultrasound for 10, 30, and 60 min respectively.The enhancement effect by this combination was increased with an increase in ultrasonic application duration, suggesting that these conditions might be used to achieve the controlled drug delivery. A pretreatment experiment with ultrasound or 5% M was carried out, and the drug content was measured to understand the role of ultrasound in the combined effect. Pretreatment of the skin with ultrasound increased the caffeine flux, while the effect of pretreatment with 5% M on the skin was similar to that of untreated skin. The results obtained suggested that simultaneous application of ultrasound and enhancers is essential to obtain the pronounced effect for transdermal as well as for topical delivery of caffeine though the skin.