Supersaturation: Enhancement of skin penetration and permeation of a lipophilic drug

Purpose, To increase the dermal delivery of a lipophilic model compound (LA P). and to deduce the underlying mechanism of enhanced absorption. Methods. Penetration of LAP from mixtures of up to four degrees of saturati on into the stratum corneum was evaluated using a tape-stripping method; ep idermal permeation of the drug was measured in Franz diffusion cells. The r elative diffusion and stratum corneum-vehicle partition coefficients of LAP were determined by fitting the results to the appropriate solutions to Fic k`s second law of diffusion. Results. Both the skin permeation rate and the amount of LAP in the stratum corneum increased linearly with increasing degree of saturation. The appar ent diffusivity and its partition coefficient deduced from the penetration experiments were independent of the degree of saturation of the drug in the applied formulation, and consistent with corresponding parameters derived from the permeation experiments. Conclusions, Supersaturation can increase the skin penetration and permeati on of lipophilic drugs. The diffusion and partition parameters deduced for LAP indicate that supersaturation acts exclusively via increased thermodyna mic activity without apparent effect on the barrier function of the skin pe r se.