Comparison of the effect of ultrasound and of chemical enhancers on transdermal permeation of caffeine and morphine through hairless mouse skin in vitro.

The effect of ultrasound (US) on permeation of two model drugs, caffeine (CAF) and morphine (MOR), through hairless mouse skin in vitro was compared with that of three chemical enhancers. Low-frequency (40 KHz), low-power (<0.5 W/cm(2)) US was used; the effect of high-frequency US (1.5-3.0 MHz) was also evaluated in the case of CAF. The chemical enhancers, tested in combination with propylene glycol (PG), were benzalkonium chloride (BAC) oleyl alcohol (OA) and alpha-terpineol (TER). The high-frequency US enhancement of CAF transdermal flux was not statistically significant, while low frequency produced a small but significant increase of the enhancement factor. The effect of US on CAF permeation, however, was lower than that produced by chemical enhancers, in particular OA. The effect of low-frequency US on permeation of MOR was significantly greater (about 10-fold) when compared, on the same frequency and intensity basis, with the effect on CAF. The most active chemical enhancer for MOR, OA, had practically the same effect as low-frequency US. Sonicated skin, although showing slight histological changes, recovered its original low permeability characteristics after turning off sonication. Within the tested system, chemical enhancement appears to offer some advantages over low-frequency US.