title: Maximum transepidermal flux for similar size phenolic compounds is enhanced by solvent uptake into the skin.
abstract: In principle, the maximum skin flux of solutes should be unaffected by the vehicle, unless that vehicle affects the skin. We recently showed that the maximum epidermal flux for 10 similarly sized phenolic compounds, with differing lipophilicities was defined by their solubility in the skin. Here, we extend these studies to examine how maximum fluxes are affected by cosolvents reported to enhance skin penetration. We compared in vitro human epidermal permeation and stratum corneum solubility for 10 phenols with similar molecular weights and hydrogen bonding but varying lipophilicity from 60% propylene glycol (PG)/water, 40% PG/water and water vehicles. We also measured solvent uptake into stratum corneum, investigated the changes in the attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy of stratum corneum and the multiphoton microscopy (MPM) images of β-naphthol for the various vehicles. We found that phenolic compounds maximum flux and stratum corneum solubilities generally increased with the percentage of PG in the binary solvent system but that the estimated diffusivities appeared to be vehicle independent. Maximum fluxes were related to vehicle-dependent stratum corneum solubilities. Theses solubilities, in turn, depended on the amount of vehicle absorbed into the stratum corneum and the amount of phenolic compounds dissolved in that absorbed vehicle. ATR-FTIR and MPM studies suggest that the vehicle-induced increased uptake of solutes into the stratum corneum occurred by an increased solubility in intercellular lipids of stratum corneum.
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide SA 5001, Australia.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000279:Administration, Cutaneous; D001692:Biological Transport; D015194:Diffusion Chambers, Culture; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D036641:Microscopy, Fluorescence, Multiphoton; D008970:Molecular Weight; D009284:Naphthols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010539:Permeability; D010636:Phenols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019946:Propylene Glycol / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D012869:Skin Absorption / Q000187:drug effects; D012995:Solubility; D012997:Solvents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
chemical_list: D009284:Naphthols; D010636:Phenols; D012997:Solvents; D019946:Propylene Glycol; C028405:2-naphthol