A Two-Phase Analysis of Solute Partitioning into the Stratum Corneum

• Published in: Journal of pharmaceutical sciences 2006-03, Vol.95 (3), p.649-666
• Main Authors: Nitsche, Johannes M., Wang, Tsuo-Feng, Kasting, Gerald B.
• Format: Article
• Language: English
• Subjects: 1-Octanol - chemistry; binding; Biological and medical sciences; corneocyte; Epidermis - cytology; Epidermis - metabolism; General pharmacology; hydration; intercellular lipid; keratin protein; Keratins - metabolism; Medical sciences; microstructure; Models, Biological; partition coefficient; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Skin Absorption; stratum corneum (SC); Water - chemistry
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.20549

An analysis is presented of partition coefficients KSC/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 Ko/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 Klip/w and a partition coefficient PCpro/w quantifying cornoeocyte-phase binding. Regression of 72 data points yields useful best-fit recalibrations of power laws (or linear free energy relationships) giving Klip/w and PCpro/w as functions of Ko/w. The specific conclusions of the analysis are as follows: (i) The two-phase model offers substantial improvements over previously proposed analytical representations of KSC/w, yielding an rms error in log10KSC/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 Klip/w=0.43 (Ko/w)0.81, suggesting about half the absolute value of Klip/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 KSC/w. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association.