Percutaneous Drug Absorption: An Evaluation of Structural & Functional Characteristics of Skin Associated with Variable Penetration of Topical Drugs.

摘要

Topicals and transdermals are some of the most widely utilized dosage forms. Despite extensive use of this type of therapy, the mechanisms of percutaneous absorption remain incompletely understood; furthermore, the degree of inter- and intra-individual variability in human skin permeability is a concern. The current study's objective was to explore possible sources of variability in skin permeability among individuals, by investigating the structural and functional properties of the skin's barrier.;To address the skin's structural properties, the effects of both corneocyte surface area and lipid content on the percutaneous absorption of drugs were studied in ex vivo trunk skin from six human subjects. To address the skin's functional properties, the same six subjects were used to study potential relationships between skin capacitance, transepidermal water loss (TEWL), and the penetration of water, octanol, and five drugs through the skin.;While cell surface area significantly correlated with measurements of skin hydration and water loss, it did not correlate with total penetration of any of the drugs tested. Conversely, total lipid content in the skin's outermost layer did show significant correlation with skin permeability to some of the drugs tested. Measurements of TEWL significantly correlated with drug penetration through the skin, while measurements of skin capacitance did not. Tritiated water flux through the skin, a measurement used historically as an indicator of skin barrier integrity, seemed to reveal more information about skin permeability to drugs than previously expected. Furthermore, the use of octanol as a hydrophobic tracer demonstrated a higher-resolved correlation with drug flux behavior through the skin. The simultaneous application of water and octanol as hydrophilic and hydrophobic tracers to assess skin permeability is a unique and novel concept. Results of the current study have demonstrated exceptional potential of its utility, and have established the groundwork for its prospective application in deconvoluting highly variable percutaneous absorption data.