Concentration-dependent enhancement of 1-dodecylazacycloheptan-2-one on the percutaneous penetration kinetics of triamcinolone acetonide

Abstract

The enhancing effect of 1-dodecylazacycloheptan-2-one (I) on the penetration kinetics of triamcinolone acetonide (II) and the possible mechanisms of enhancement were studied using nonreinforced and reinforced silicone elastomer membranes and full-thickness hairless mouse skin as penetration barriers. Lactam I, at test concentrations of 0.1-10%, significantly promoted the extent and the rate of penetration of the acetonide II. Regardless of the barrier used the effect was concentration dependent, but the penetration profiles were different. The enhancement with synthetic membranes was attributed solely to the effect of lactam I doubling the diffusion constant (D), which resulted in the increase of the permeability coefficient (Kp) and the shortening of the lag time (tau); the partition coefficient (Km), however, was not affected. With mouse skin, I exerted effects on both D and Km. Compound I potentiated the retention of II in skin (a reservoir effect) about sevenfold; however, the enhancing reservoir effect was independent of the concentration of I. Pretreatment with I was found to be more efficient than the coapplication of I and II in the vehicle. The coexistence of I and II was not required for the enhancement, and the reduced enhancing efficiency suggested an interaction between I and II in the vehicle. Penetration impedance was observed after exposure to I with skin, but not with synthetic membranes. Interaction of I with the skin component, or the coexistence of I and II in the skin, could be responsible for such an impedance.