A lamellar matrix model for stratum corneum intercellular lipids. II. Effect of geometry of the stratum corneum on permeation of model drugs 5-fluorouracil and oestradiol

Abstract

The principal barrier to transdermal delivery of most drugs is the lamellar intercellular lipid domain of the stratum corneum (SC). The low permeability of SC in comparison to other lipid barriers is in part due to its geometry. Here, effect of geometry of the SC on permeation of 5-fluorouracil (5-FU) - a model hydrophilic drug - and oestradiol (OE) - a model lipophilic drug - was investigated using a lamellar model matrix for SC intercellular lipids. Release studies at 32°C showed that the diffusion coefficients of 5-FU and OE in the matrix are approximately 6000 —7000 and 60–260-times greater, respectively, than apparent human epidermis values, in good agreement with theoretical considerations. Release studies from 13 to 44°C revealed that 5-FU has a maximum diffusion coefficient around the main transition temperature of the matrix (35°C) in agreement with other lamellar systems reported in the literature. The diffusional activation energy of 5-FU in the matrix was 27.8 kcal mol −1 which correlates well with human epidermal data. Release experiments were then combined with permeation studies and the permeability of model drugs through the SC at 32°C was predicted from matrix data. The predicted permeability coefficients of 5-FU (5.5–18 × 10 −5 cm h −1) and OE (0.07-0.24 × 10 −3 cm h −1) were in agreement with human epidermis data. Our results show the effect of the SC morphology on the percutaneous absorption of drugs and illustrate that 5-FU and OE permeate the SC through intercellular lipids.