title: A quantitative radioluminographic imaging method for evaluating lateral diffusion rates in skin.
abstract: A method is presented for measuring the lateral diffusion coefficients of exogenously applied compounds on excised skin. The method involves sequential high resolution imaging of the spatial distribution of β-radiation associated with [(14)C]-labeled compounds to monitor the development of the concentration profile on the skin surface. It is exemplified by measurements made on three radiolabeled test compounds--caffeine, testosterone, and zinc pyrithione (ZnPT)--administered as solutions. Lateral diffusivity is expected to be an important determinant of the topical bioavailability of ZnPT, which is characteristically administered as a fine suspension and must reach microorganisms in molecular form to exert biocidal activity. Application of the test compounds at levels below and above their estimated saturation doses in the upper stratum corneum allows one to distinguish between diffusion-limited and dissolution rate-limited kinetics. The effective lateral diffusivities of the two chemically stable reference compounds, caffeine and testosterone, were (1-4) × 10(-9) cm(2)/s and (3-9) × 10(-9) cm(2)/s, respectively. Lateral transport of [(14)C] associated with ZnPT was formulation-dependent, with effective diffusivities of (1-2) × 10(-9) cm(2)/s in water and (3-9) × 10(-9) cm(2)/s in a 1% body wash solution. These differences are thought to be related to molecular speciation and/or the presence of a residual surfactant phase on the skin surface. All values were greater than those estimated for the transverse diffusivities of these compounds in stratum corneum by factors ranging from 250 to over 2000. Facile lateral transport on skin, combined with a low transdermal permeation rate, may thus be seen to be a key factor in the safe and effective use of ZnPT as a topical antimicrobial agent.
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45267, USA.
authors.forename: Allison K
authors.initials: AK
authors.lastname: Rush
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45267, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Miller
authors.affiliation: The Procter & Gamble Company, Cincinnati, OH, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Smith
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH 45267, USA. Electronic address: Gerald.Kasting@uc.edu.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Kasting
mesh_terms: D001610:Beta Particles; D001682:Biological Availability; D001693:Biological Transport, Active; D002110:Caffeine / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D004058:Diffusion; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D049449:Luminescence; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D012867:Skin / Q000737:chemistry*; D012869:Skin Absorption; D012996:Solutions; D013739:Testosterone / Q000493:pharmacokinetics
chemical_list: D002250:Carbon Radioisotopes; D009942:Organometallic Compounds; D011725:Pyridines; D012996:Solutions; D002110:Caffeine; D013739:Testosterone; C010423:pyrithione zinc
keywords: Antimicrobial; Caffeine (PubChem CID:2519); Dissolution; Molecular imaging; Phosphorimaging; Stratum corneum; Testosterone (PubChem CID:6013); Topical bioavailability; Zinc pyrithione (PubChem CID:26041)