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 Laurocapr am (Atone) on the skin permeation of were conducted. Partitioning of a n homologous series of alkyl anilines into drugs, the following experi ments was n-octanol and isopropyl myristate (IPM) in the absence and p resence 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 in creased the ounced for 10% Atone in both cases. The partition coeffici ents 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 alky l anilines (aniline, 4-ethylaniline, 4-n-butylaniline and 4-n-pentylan iline) with a wide range of lipophilicity values (log PCOct from -0.87 to 4.2 where PCOct is the octanol water partition coefficient) and tw o compounds which belong to the phenyl alkanols series, 2-phenylethano l and 4-phenylbutanol with lipophilicity values of log PCOct of 1.18 a nd 2.34, respectively. The enhancer effect of Atone depended predomina ntly 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 lip ophilicity value of less than log PCOct of 1 but if the enhancer conce ntration was increased to 5% (w/w) this lipophilicity threshold increa sed 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 th e higher concentration. The less the lipophilicity value of the penetr ant, the greater the enhancer effect observed. In tile case of 10% Ato ne the penetration of the compounds tested could be also increased for 5-FU, aniline. 4-ethylaniline, 2-phenylethanol and 4-phenylbutanol, b ut for this last compound there is a reduction in the degree of penetr ation if it is compared with the permeability coefficients obtained wi th 5% of Atone. Finally, the Atone cannot enhance the skin permeabilit y for the highest lipophilic compounds (log PCOct greater than or equa l to 3).