The relative effect of Azone and Transcutol on permeant diffusivity and solubility in human stratum corneum.
OBJECTIVE
The purpose of this work was to analyse the mechanism of the enhancement of percutaneous penetration demonstrated by the known enhancers Azone and Transcutol.


METHODS
Enhancer induced changes in the diffusivity and solubility of a model permeant (4-cyanophenol) in human stratum corneum were monitored (in-vitro) using Attenuated total reflectance Fourier transform infra-red (ATR-FTIR) spectroscopy and compared to the gross effects of the enhancers on flux as measured using simple Franz-type diffusion cells.


RESULTS
It has been shown by both the well-established Franz diffusion cell technique and the use of ATR-FTIR spectroscopy that the enhancers studied both increase the flux of cyanophenol across human skin in-vitro by a factor of approximately two. Furthermore, it has been demonstrated by ATR-FTIR that these enhancers are likely to exert their effects by different mechanisms. It is probable that Azone reduces the diffusional resistance of the stratum corneum and that Transcutol increases the solubility of the penetrant in this barrier.


CONCLUSIONS
There is increasing interest in the apparently synergistic nature in which certain enhancers appear to work. The exact nature of these multiplicative and/or additive effects is not known although there are numerous suggestions in the current literature. The application of ATR-FTIR spectroscopy to such enhancing systems will allow the mechanisms of the observed enhancements to be probed in greater depth.
Harrison
J E
JE
Welsh School of Pharmacy, UWCC, Cardiff, United Kingdom.
Watkinson
A C
AC
Green
D M
DM
Hadgraft
J
J
Brain
K
K
D000704:Analysis of Variance; D001381:Azepines / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D005026:Ethylene Glycols / Q000494:pharmacology*; D006801:Humans; D016014:Linear Models; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism*; D010636:Phenols / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
D001381:Azepines; D005026:Ethylene Glycols; D008996:Monoamine Oxidase Inhibitors; D010636:Phenols; C035229:laurocapram; C007178:4-cyanophenol; C010111:carbitol