A two-phase analysis of solute partitioning into the stratum corneum.
An analysis is presented of partition coefficients K(SC/w) describing solute distribution into fully hydrated stratum corneum (SC) from dilute aqueous solution (w). A comprehensive database is compiled from the experimental literature covering more than eight decades in the octanol/water partition coefficient K(o/w). It is analyzed according to a two-phase model following that of Anderson, Raykar, and coworkers (1988, 1989), which accounts for uptake by intercellular lipid and corneocyte (keratin plus water) phases having inherently different lipophilicities, as characterized by an SC lipid/water partition coefficient K(lip/w) and a partition coefficient PC(pro/w) quantifying cornoeocyte-phase binding. Regression of 72 data points yields useful best-fit recalibrations of power laws (or linear free energy relationships) giving K(lip/w) and PC(pro/w) as functions of K(o/w). The specific conclusions of the analysis are as follows: (i) The two-phase model offers substantial improvements over previously proposed analytical representations of K(SC/w), yielding an rms error in log(10)K(SC/w) of 0.30 limited by the scatter in the data. (ii) The best-fit description of the lipid phase is given by the power law K(lip/w) = 0.43 (K(o/w))(0.81), suggesting about half the absolute value of K(lip/w) relative to previous estimates. (iii) The best-fit description of corneocyte-phase binding differs negligibly from the correlation found by Anderson, Raykar, and coworkers for the more limited set of compounds studied by them. Explicit consideration of the two-phase nature of the SC also furnishes a rational basis for predicting the effects of varying hydration state upon K(SC/w).
Nitsche
Johannes M
JM
Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, 14260-4200, USA.
Wang
Tsuo-Feng
TF
Kasting
Gerald B
GB
D020003:1-Octanol / Q000737:chemistry*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism*; D008954:Models, Biological; D012869:Skin Absorption; D014867:Water / Q000737:chemistry*
D014867:Water; D007633:Keratins; D020003:1-Octanol