Permeation of hydrocortisone and hydrocortisone 21-alkyl esters through silicone rubber membranes -- relationship to regular solution solubility behavior

Abstract

Rates of permeation of 75 [mu]m thick silicone rubber membranes by hydrocortisone and six homologous hydrocortisone 21-alkyl esters, all applied to the membranes in aqueous media, were assessed in small glass diffusion cells. Solubilities of these agents in water and hexane were also determined. The permeability coefficient of hydrocortisone was 7.4 x 10-5 cm/hr. Permeability coefficients for the esters ranged from 2.3 x 10-3 cm/hr (acetate) to 6.4 x 10-1 cm/hr (heptanoate). A direct correlation was found between permeability coefficients and lipophilicity but it appears that the heptanoate eater's mass transfer coefficient is substantially boundary layer controlled. Assessment of fluxes of the steroid solutes from their respective saturated aqueous solutions was made. The flux for hydrocortisone through silicone rubber was greater than the flux for the acetate ester. Thereafter, fluxes of the esters from saturated solutions systematically increased to the point where fluxes for the 21-hexanoate and 21-heptanoate esters were 20 times greater than found for hydrocortisone. This suggests that far more steroid can be delivered through a lipid membrane when the steroid is appropriately derivatized. The overall permeability pattern fits behavior expected of a barrier having a lipid membrane bounded by hydrodynamic layers. The pattern of permeability from saturated solutions was predictable using regular solution theory.