Effect of ultrasound on transdermal permeation of diclofenac and the temperature effects on human skin
During the last two decades the effects of ultrasound on the transdermal diffusion of a wide variety of drugs have been extensively investigated. Because there is much uncertainty regarding the efficacy of and mechanisms involved in this mode of permeation enhancement, the objective of the study was to investigate the effect of ultrasound on the transdermal permeation of the nonsteroidal anti-inflammatory drug, diclofenac. For this purpose a dual-stage experimental design and a continuous flow-through diffusion system was used. Therapeutic levels of continuous ultrasound of 3 MHz at an intensity of 2 W/cm2 for 10 min, were used. It was clear from the present study that ultrasound enhanced the permeability of human skin to diclofenac released from a commercially available gel. These results were in contrast with those obtained for ibuprofen in an in vitro study across human skin, but in agreement with those obtained in two in vivo studies of the latter nonsteroidal anti-inflammatory drug. Steady state flux values of diclofenac remained approximately 1.26 times higher than those of controls during the 24 h of the experiment. These observations concurred with those made in two previous in vivo studies. Furthermore, the in vitro flow-through diffusion model was shown to have predictive value as an in vivo method for sonophoresis. Temperature-dependent flux rates for 3H2O across human skin were also studied. The mechanistic effects of ultrasound on the permeability characteristics of human skin have been reported on in a number of studies. Although various mechanisms have been proposed, there is no consensus regarding their relative importance. In addition the temperature-dependent flux changes of 3H2O across human skin were investigated using a continuous flow-through diffusion system. The same ultrasound parameters as in the permeability experiments were used. The results obtained showed that temperature increases of approximately 10 °C occurred following sonication. The flux changes of 3H2O across human skin between 37 °C and 42 °C were shown to be reversible. The results from the present study do not support the sonication-heating theory in which permeability changes in skin are primarily attributed to thermally-induced changes in stratum corneum lipids. It was therefore concluded that the enhancement of diclofenac permeation by sonication could not be adequately explained primarily on a thermal basis.