[Transdermal Drug Delivery Systems: From the Dawn and Early Stage to the Development and Maturity Stage, and the Future].

This review describes the analytical methods for percutaneous absorption and skin permeation of chemical substances and the transdermal drug delivery system (TDDS) that I have been researching for about half a century. This period coincides with that of the dawn and early stage of TDDS through its development to the maturity stage. First, as an introduction, the skin structure, definitions of scientific terms such as percutaneous absorption, skin permeation, skin penetration, types of chemical substances that make contact with the skin, and the skin permeation pathway of chemical substances are outlined. Next, the experimental methods established for percutaneous absorption and skin permeation of chemical substances are described. Then, analytical methods for the percutaneous absorption rate are outlined: i.e., partition to skin barrier and diffusion in the stratum corneum of chemical substances, the meaning of the permeability coefficient, and Fick's 1st and 2nd laws of diffusion. Furthermore, after showing the modeling of the skin barrier as a diffusion layer, the analytical method of skin concentration is also explained. In addition, after explaining the concept of thermodynamic activity of chemical substances for percutaneous absorption, the usefulness of skin-penetration enhancers and physical means to increase skin permeation is reviewed. Finally, I introduce my dream of an installable DDS on or in the skin in future therapeutic modalities.