Skin Permeation of Urea Under Finite Dose Condition.

In a previous study investigating the relationships between solute physicochemical properties and solvent effects on skin permeation of solutes under finite dose conditions, urea was found to have the highest percent dose absorbed among the model solutes studied. The objective of this study is to probe the mechanism of the observed high skin permeation of urea at finite dose, in contrast to its permeability coefficient obtained under infinite dose condition. Skin permeation experiments were performed with Franz diffusion cells and human epidermal membrane. Dose-dependence and penetration enhancing effects of urea permeation were investigated. Tape stripping was performed. A small hydrophilic solute ethylene glycol with molecular weight similar to urea was studied for comparison. The results suggest that urea did not have penetration enhancing effect to enhance solute permeation across skin under the finite dose conditions. Tape stripping data are consistent with skin permeation mechanism of solute deposition and diffusion. The skin permeation behavior of urea could be attributed to its small molecular size. This suggests that, under the finite dose conditions examined in this study, solutes with molecular sizes similar to or less than urea and ethylene glycol could lead to high percent of skin absorption despite their hydrophilicities.

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

The 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.

Effects of solvent on percutaneous absorption of nonvolatile lipophilic solute.

Understanding the effects of solvents upon percutaneous absorption can improve drug delivery across skin and allow better risk assessment of toxic compound exposure. The objective of the present study was to examine the effects of solvents upon the deposition of a moderately lipophilic solute at a low dose in the stratum corneum (SC) that could influence skin absorption of the solute after topical application. Skin permeation experiments were performed using Franz diffusion cells and human epidermal membrane (HEM). Radiolabeled corticosterone ((3)H-CS) was the model permeant. The solvents used had different evaporation and skin penetration properties that were expected to impact skin deposition of CS and its absorption across skin. The results show no correlation between the rate of absorption of the permeant and the rate of solvent evaporation/penetration with ethanol, hexane, isopropanol, and butanol as the solvent; all of these solvents have fast evaporation rates (complete evaporation in <30 min after application). This suggests no differences in solvent-induced deposition of CS in the SC for the fast-evaporating solvents. The results of these fast-evaporating solvents were different from those of water, propylene glycol, and polyethylene glycol 400, that a relationship between permeant absorption and the rate of solvent evaporation was observed.