INFLUENCE OF THE PERMEATION ENHANCERS 1-ALKYL-2-PYRROLIDONES ON PERMEANT PARTITIONING INTO THE STRATUM-CORNEUM

In a previous study, the enhancing effects of a series of 1-alkyl-2-py rrolidones (APs; 1-ethyl, 1-butyl, 1-hexyl, and 1-octyl-2-pyrrolidone) on the transport of steroidal permeants across hairless mouse skin we re investigated via a parallel pathway skin model. Isoenhancement conc entration conditions were deduced under which different APs induce ess entially the same transport enhancement for the lipoidal pathway of th e stratum corneum (SC). As a continuing effort to understand the mecha nism of action of permeation enhancers, the influence of the APs on pe rmeant partitioning into hairless mouse SC was investigated under the isoenhancement concentration conditions using beta-estradiol (E2 beta) as the model permeant. The amount of E2 beta uptake into SC was found to be essentially the same for all the APs under these isoenhancement conditions. This result suggests that inducing a higher partitioning tendency for E2 beta into the lipoidal pathway of hairless mouse SC is a principal mechanism of action of the APs in enhancing transdermal t ransport. The uptake of the APs into SC lipoidal domains was also dete rmined, and the results show only a modest (approximately 2-fold) incr ease in the uptake of the APs in going from 1-ethyl- to 1-octyl-2-pyrr olidone under isoenhancement conditions. This indicates the potency of the APs as permeation enhancers is only very modestly dependent upon the alkyl chain length in this chain length region when compared at co ncentrations in the microenvironment where the action occurs in the li pid domains.