Human skin permeation and partition: General linear free-energy relationship analyses

✍ Scribed by Michael H. Abraham; Filomena Martins

• Book ID: 102400020
• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 161 KB
• Volume: 93
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.20070

✦ Synopsis

Literature values of the permeability coefficient for permeation of human skin from water have been adjusted for ionization in water and adjusted for temperature. The obtained values of log K p for 119 solutes at 378C have been correlated with Abraham descriptors to yield an equation with R 2 ¼ 0.832 and SD ¼ 0.46 log units. Three separate test sets of 60 compounds had log K p predicted with an SD of 0.48 log units. The main factors that influence log K p are solute hydrogen bond basicity that lowers the permeability coefficient and solute volume that increases the permeability coefficient. Human skin-water partition coefficients, as log K sc , have been collected for 45 compounds and yield an equation with R 2 ¼ 0.926 and SD ¼ 0.22 log units. We have compared the log K p equation to equations for various other processes, but have found no process that appears to be similar to that for skin permeation. The nearest process to skin-water partition is the isobutanol-water partition system. An equation for lateral diffusion in the stratum corneum is shown to be reasonably close to various diffusion-related processes.