Effects of solvents on skin absorption of nonvolatile lipophilic and polar solutes under finite dose conditions

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Graphical abstractThe effects of solvents upon the deposition of a moderately lipophilic solute on skin and skin permeation were investigated previously. The present study was a continuing effort to investigate the effects of solvents on finite dose skin absorption of nonvolatile lipophilic and polar solutes and examine the relationships between solute physicochemical properties, solvent effects, and skin absorption of these solutes after solvent deposition. Skin permeation experiments under the finite dose conditions were conducted with model solutes (corticosterone, urea, mannitol, glycerol, triamcinolone acetonide, and estradiol) and model solvents (ethanol, butanol, water, and propylene glycol) using Franz diffusion cells and human epidermal membrane. Urea showed unexpectedly high skin permeation under the finite dose conditions compared to the other solutes based on their skin permeability coefficients (obtained under infinite dose condition). The influences of the solvents on solute permeation suggest that these solvents did not act solely as a vehicle for spreading the solutes during solvent deposition. In the testing of skin permeation mechanisms, model analyses indicated a correlation between solute permeation and their molecular weights and solubilities, suggesting that the solute permeation mechanism with the volatile solvent was related to solute dissolution on the skin surface and its diffusion across the skin.

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