Pharmacokinetic modeling and penetration enhancement of the percutaneous drug absorption based on diffusion theory

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Two-layer skin model considering the first stratum corneum layer with polar and nonpolar routes and the second viable epidermis plus dermis layer was constructed and the corresponding transformed equations in the infinite and finite dose systems were derived from the Fick's diffusion low. By employing the inversion of these image equations to the real time course by the fast inverse Laplace transform(FILT)algorithm, absorption behavior of drugs were analyzed from physicochemical viewpoint. Using this system, the effects of different doses of 1-geranyl-azacycloheptan-2-one(GACH)on the in vitro penetration of seven drugs with various lipophilicities through the guinea pig skin were examined and its action mechanism wasdiscussed in terms of the partitioning and diffusivity of drugs in each domain. It was suggested that GACH mainly affects on the nonpolar route of the stratum corneum by changing its property as a solvent. The effects of d-limonen and oleic acid were also analyzed and the were concluded to enhance drug absorption by increasing the diffusivity of the drug in the stratum corneum. A skin diffusion model corresponding to in vivo condition was also constructed and relationship between in vitro and in vivo data was discussed based on these models.