Effect of therapeutic ultrasound on partition and diffusion coefficients in human stratum corneum

Application of various enhancers including ultrasound and chemicals has been shown to enhance transdermal drug transport. Most of these enhancers increase transdermal transport by increasing either partition or diffusion coefficients in lipid bilayers. Although the effect of such enhancers on skin permeability has been measured in many cases, the effect of the same enhancers on solute partition and diffusion coefficients has not been measured since such measurements are difficult. In this paper, we describe application of a new method that can be used to determine the effect of enhancers on partition and diffusion coefficients. This method is based on two independent measurements of the transport properties of the SC and a theoretical model. This method was tested for five solutes including estradiol, napthol, aldosterone, lidocaine, and testosterone. Measurements based on our method showed that the primary effect of therapeutic ultrasound (1 MHz) is on diffusion coefficient and not partition coefficient. Specifically, ultrasound enhanced diffusion coefficients of these solutes by up to 15-fold. However, it did not significantly enhance partition coefficients. The method described in this paper is quite general and can be used to measure the effect of various enhancers on partition and diffusion coefficients.