Solvent drag in ethanol/ethyl acetate enhanced skin permeation of d-norgestrel

Abstract

The relationship between the transdermal flux through hairless mouse skin of a solute ( d-norgestrel) and two solvents (ethanol and ethyl acetate) at apparent steady state was studied using irreversible thermodynamics. To accomplish this, a model was developed based on the linear relationship between fluxes and forces related through a phenomenological coefficient. The model relates the flux of d-norgestrel to its uncoupled flux, the positive contributions of solvent (ethanol and ethyl acetate) flux, and the negative contribution of reverse water flux. The phenomenological coefficients relating drug and solvents flows were calculated from the permeation data through hairless mouse skin. It was found that the coefficients for solvent drag from ethanol and ethyl acetate were approximately equal; however, these coefficients were very small and hence insignificant. It was also found that the contribution of negative water flux from the receiver chamber to the donor vehicle leads to a relatively minor negative drag on the flux of d-norgestrel through hairless mouse skin. The implications of the model are discussed in terms of the existing knowledge about the function of skin and the inherent limitations of a phenomenological approach.