A mechanistic investigation of the in vitro human skin permeation enhancing effect of Atone(R)

In order to clarify the mechanism of the enhancing action of Laurocapram (Atone) on the skin permeation of were conducted. Partitioning of an homologous series of alkyl anilines into drugs, the following experiments was n-octanol and isopropyl myristate (IPM) in the absence and presence of Atone (1%, 5%, and 10%, w/w) determined. The addition of 1% and 5% of enhancer to n-octanol and 1% of enhancer to IPM slightly increased the ounced for 10% Atone in both cases. The partition coefficients of the alkyl anilines assayed. This effect was more pron of Atone for similar concentrations through investigated using 5-fluorouracil as a hydrophilic model permeant, four compounds selected from the alkyl anilines (aniline, 4-ethylaniline, 4-n-butylaniline and 4-n-pentylaniline) with a wide range of lipophilicity values (log PCOct from -0.87 to 4.2 where PCOct is the octanol water partition coefficient) and two compounds which belong to the phenyl alkanols series, 2-phenylethanol and 4-phenylbutanol with lipophilicity values of log PCOct of 1.18 and 2.34, respectively. The enhancer effect of Atone depended predominantly on two parameters, the concentration of the enhancer used and the lipophilicity of the compound assayed. When the concentration of the Atone employed was 1% (w/w), it only acted on the compounds with a lipophilicity value of less than log PCOct of 1 but if the enhancer concentration was increased to 5% (w/w) this lipophilicity threshold increased to a log PCOct value of 2.69. Therefore the number of drugs whose penetration may be increased by the use of Atone will be greater at the higher concentration. The less the lipophilicity value of the penetrant, the greater the enhancer effect observed. In the case of 10% Atone the penetration of the compounds tested could be also increased for 5-FU, aniline. 4-ethylaniline, 2-phenylethanol and 4-phenylbutanol, but for this last compound there is a reduction in the degree of penetration if it is compared with the permeability coefficients obtained with 5% of Atone. Finally, the Atone cannot enhance the skin permeability for the highest lipophilic compounds (log PCOct greater than or equal to 3).