MECHANISTIC STUDIES OF THE 1-ALKYL-2-PYRROLIDONES AS SKIN PERMEATION ENHANCERS

The influences of 1-ethyl-, 1-butyl-, 1-hexyl-, and 1-octyl-2-pyrrolid one in their saline solutions on the transport of beta-estradiol, cort icosterone, and hydrocortisone across hairless mouse skin under in vit ro conditions have been investigated by the physical model approach. T he experimental data were interpreted with a physical model that treat s the stratum corneum as a diffusional barrier with a lipoidal pathway and a pore pathway. Enhancement factors (E values) for the lipoidal p athway were calculated from the permeability coefficients and solubili ty data as a function of the 1-alkyl-2-pyrrolidone concentration for a ll three permeants. A pattern of increasing E values with increasing 1 -alkyl-2-pyrrolidone chain length was found, and the results were esse ntially the same for all three steroidal permeants. A nearly semilogar ithmic linear relationship was also obtained between the enhancement p otency and the carbon number of the alkyl chain; there was about an si milar to 3.5-fold increase in the enhancement potency per 1-alkyl-2-py rrolidone methylene group. An important outcome of this research is th at the enhancement potencies of the 1-alkyl-2-pyrrolidones were essent ially the same as those for the previously studied n-alkanols when com pared at the same carbon numbers of the alkyl groups, This result is s omewhat surprising as it suggests that the enhancer action resides (in its entirety) in the alkyl group, and the nature of the polar head gr oup may not be intrinsically important in transdermal enhancement of t he lipoidal pathway within a class of permeation enhancers.