Polar solute transport across skin

Recent developments in the areas of chemical permeation enhancers and iontophoresis have led to the potential transdermal delivery of polar and ionic solutes. With these developments comes a need to better characterize the routes of penetration for these solutes. A fundamental understanding of the skin barrier function should lead to more rational approaches in transdermal drug delivery system development. The initial challenges and achievements in this dissertation were related to development of experimental methodologies that enabled studies to be performed that facilitated quantitative data analysis and interpretation. It was established that successive permeation experiments with a single human epidermal membrane sample eliminated many of the experimental obstacles associated with performing quantitative transdermal permeation research. Human epidermal membrane samples supported with synthetic porous membrane in the diffusion cells retained initial barrier properties for extended periods of time, making successive permeation studies possible. With an adequate experimental methodology in hand, a series of studies aimed at probing the barrier properties of human epidermal membrane with respect to polar solute permeation was conducted. These studies were designed based upon testing expectations for permeation characteristics of a porous permeation model. The concepts of effective pore size, influence of temperature upon permeation, correlation between solute flux and ion conduction under an applied electrical field, and importance of permeant molecular size upon flux enhancement due to electro-osmosis during iontophoresis, were established using a well-characterized model membrane system and tested for human epidermal membrane. It was shown that the experimental human epidermal permeation data for polar solutes from each set of studies strongly supported the concept of a porous permeation pathway through the stratum corneum. Furthermore, this pathway was characterized by pore dimensions on the order of 15 A. The methodologies developed were applied in assessing the effects of sodium dodecyl sulfate upon the transdermal passive and iontophoretic flux of polar solutes. It was shown that whereas the surfactant had only minor effects upon effective pore size of the membrane, it significantly enhanced the intrinsic permeability of the membrane and electro-osmotic solvent flow during iontophoresis.