Keratinized epithelial transport of beta-blocking agents. II. Evaluation of barrier property of stratum corneum by using model lipid systems.

Model lipid mixtures composed of ceramide (40%), cholesterol (25%), palmitic acid (25%) and cholesterol 3-sulfate (10%) were used as the model for intercellular lipids of stratum corneum (SC) to evaluate a barrier function of SC for drug permeation. Six beta-blockers, propranolol, metoprolol, timolol, pindolol, nadolol and atenolol, were used as the model permeants. The maximum flux values (observed flux/thermodynamic activity, Jmax) of drugs through the membrane coated with the model lipid mixtures and two keratinized membranes, rat skin and hamster cheek pouch, were determined in vitro using a Franz-type diffusion cell. Further, drug partition coefficients to the multilamellar liposomes prepared by the model lipid mixtures were determined. The Jmax values obtained in the model lipid-coated membrane, in the intact rat skin and in the intact hamster cheek pouch mucosa, bore a linear relationship to each other. These results suggest that the model lipid-coated membrane is a useful tool for the prediction of the drug permeability through the keratinized membrane in the in vitro system. The Jmax values also correlated with drug partition to the model lipid liposomes, suggesting the validity of the use of the model lipid mixtures as the substitutes for the intercellular lipids of the stratum corneum.