The epidermis is continuously exposed to deleterious external stimuli, such as ultraviolet irradiation, dryness, mechanical stress, xenotoxic chemicals and microbial pathogens, and it deploys multiple barriers to protect internal tissues as well as the skin from these insults to maintain normal cellular functions. The epidermis consists of four layers - stratum basale, stratum spinosum, stratum granulosum and enucleated stratum corneum. The stratum corneum deploys most barriers, and it is the lipids in the stratum corneum that play a critical role in forming the epidermal permeability barrier. In particular, in the stratum corneum, ceramide is the lipid, made up of heterogeneous molecules not reported in other tissues, that is essential for barrier formation. Ceramide metabolites also contribute to formation of a competent permeability barrier formation. Additionally, these ceramide metabolites in the nucleated layers of the epidermis serve as modulator lipids in the formation of the antimicrobial barrier through increasing antimicrobial peptide production.

Stratum Corneum (SC) is the outer most thin layer of our body with merely 10 to 30 μm, controlling in- and outbound material trafficking as a barrier for the survival. SC consists of corneocyte, symbolized as brick, and SC intercellular lipids (SCL), symbolized as mortal. SCL exists as hydrated pseudo solid lamellar gel composed of ceramide, cholesterol and free fatty acid distinctive from any other bio-membrane. This review introduces structure and functions of SCL as a major skin barrier in view of physicochemical aspects.

In order to further develop topical dosage preparation and transdermal drug delivery systems (TDDS) as a convenient DDS, it is necessary to fully understand the skin structure and the percutaneous absorption of drugs. Here, the author explained skin penetration pathway of drugs and kinetics aspect for the percutaneous absorption of drugs as well as skin concentration profiles, which are important especially for evaluation of topical dosage preparation. In addition, the author explained about the use of skin-penetration enhancers and physical means to increase the skin permeation of drugs, which are important in practical application. Great progress of AI (artificial intelligence) and IoT (internet of things) may derive completely new types of TDDS in the near future. That is why it is time to look back on the past for the sake of the future.

Transdermal patches both of topical and systemic use is a useful and user friendly pharmaceutics. Poultice containing ketoprofen features the cross-linking network between aluminum and sodium polyacrylate and is a swollen hydrogel. Large amount of drug, water and other additives can be contained in the poultice. Ketoprofen is easily released from poultice and absorbed into the skin. In addition, microdialysis technique is used for evaluation of percutaneous penetration of ketprofen in pigs. These results show the topical patches containing ketprofen can deliver the drug through the skin and knee joint via direct diffusion. It was found that poultice containing ketoprofen is a useful and user friendly formulation for patients. Adhesives are one of important excipients for development of systemic transdermal patches. Newly developed acrylic adhesive (AAEM-ad) could contain lots of liquid substance with sufficient cohesion and had the properties of high release rate and skin permeation. The bioequivalence is shown between original product and AAEM-ad patch containing tulobuterol. New adhesion tests are listed in Japanese pharmacopoeia 17th edition such as peel test, ball tac test, rolling ball tac test and probe tac test, the same as drug release test for seeking a high evidence of patches.

Microneedle arrays are micron-scale needles assembled on a transdermal patch. They are a novel and minimally invasive approach for transdermal drug delivery, and are capable of creating su perficial pathways across the skin for small drugs and macromolecular drugs, including peptide and protein drugs, to achieve enhanced drug delivery. Since Henry et al. have reported the microneedle arrays in the field of transdermal absorption in the 1990’s, microneedle arrays have been fabricated from numerous materials and in a variety of shapes and sizes, for the transdermal drug delivery. In this review, we summarized the studies of microneedle arrays as new type of transdermal formulation in terms of development history, pharmaceutical characteristics and recent challenges. Future pros pects of microneedle arrays are also discussed from viewpoint of clinical application.