Document Detail


Drug permeation through human skin II: Permeability of ionizable compounds.
MedLine Citation:
PMID:  6502479     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to establish whether ionized as well as un-ionized forms of certain 4-oxo-4H-1-benzopyran-2-carboxylic acids (chromone-2-carboxylic acids) with pKa values less than 2 permeated through excised human skin and, if so, to determine the permeability coefficients of the permeating species. The permeation properties of four carboxylic acids were studied as a function of concentration over the pH range 5-7 at 37 degrees C with plexiglass diffusion cells. Plots of J/CA- (the total flux due to un-ionized and ionized species obtained under steady-state conditions per unit concentration of ionized drug in the donor compartment) against CH3O+ resulted in straight-line relationships. The intercepts of these plots were shown to equal PA-, whereas the slopes multiplied by the Ka values of the compounds equalled PHA, the permeability coefficients of the ionized and un-ionized species, respectively. With all four compounds, both species were found to permeate skin, although the permeability coefficients of the un-ionized species were approximately 10(4) greater than those for the ionized species. It was demonstrated that the relative contributions of the ionized and un-ionized species to the total flux, as well as the total flux, vary significantly, depending on the pH of the drug solution in the donor cell. This may provide a means of controlling the flux of these and similar compounds through human skin.
Authors:
J Swarbrick; G Lee; J Brom; N P Gensmantel
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  73     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  1984 Oct 
Date Detail:
Created Date:  1985-01-09     Completed Date:  1985-01-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1352-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Chromatography, High Pressure Liquid
Chromones / metabolism
Humans
Hydrogen-Ion Concentration
Kinetics
Permeability
Pharmaceutical Preparations / metabolism*
Skin Absorption*
Solubility
Chemical
Reg. No./Substance:
0/Chromones; 0/Pharmaceutical Preparations; 4940-39-0/chromone-2-carboxylic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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