Dose-dependent effect on skin permeation of polar and non-polar compounds.

The study of the relationship between the amount of drug applied to the skin and fraction of drug absorbed can improve our understanding of finite-dose percutaneous absorption in the development of topical products and risk assessment of hazardous chemical exposure. It has been previously shown that an increase in the dose applied to the skin leads to a decrease in the fraction of drug permeated the skin (dose-dependent effect). The objective of this research was to examine the dose-dependent effect using permeants of varying physiochemical properties. The dose-dependent effect was studied using human epidermal membrane under finite dose conditions in Franz diffusion cell with model permeants at doses ranging from 0.1 to 200 µg. The dose-dependent effect was evident with model permeants caffeine, corticosterone, dexamethasone, and estradiol, consistent with the relationship of decreasing fraction of dose permeated the skin at increasing the applied dose. However, no significant dose-dependent effect was observed for the polar model permeants urea, mannitol, tetraethyl ammonium, and ethylene glycol, suggesting different transport mechanisms for these permeants. It was also found that, at relatively high doses, estradiol, dexamethasone, and corticosterone could increase the permeation of polar and lipophilic permeants, which could counter the dose-dependent effect under the conditions studied.

Effect of Receptor Solution in Studies of In Vitro Permeation Test (IVPT).

In Vitro Permeation Test (IVPT) is commonly used to evaluate skin penetration of chemicals and performance of dermatological products. For a permeant with low aqueous solubility, an additive that is expected not to alter the skin barrier can be used in the receptor solution to improve permeant solubility. The objective of this study was to (a) evaluate the effects of these additives in IVPT receptor solution on skin permeability of model permeants and skin electrical resistance and (b) determine the solubility of the permeants in these receptor solutions. Bovine serum albumin (BSA), 2-hydroxypropyl-beta-cyclodextrin (HPCD), ethanol, nonionic surfactant Brij-98, and propylene glycol were the additives, and phosphate buffered saline (PBS) was the control. Steady-state skin permeability coefficients and resistances were determined. The receptor solutions examined in this study did not cause a significant increase in skin permeability or decrease in resistance (less than 40 % changes) except 25 % ethanol. The receptor solution containing 25 % ethanol induced an approximately twofold average increase in skin permeability and reduced skin electrical resistance by approximately threefold. The receptor solution of 2.5 % HPCD provided the highest levels of solubility for the model lipophilic permeants, while 0.2 % Brij-98 and 5 % ethanol showed the lowest solubility enhancement from those in PBS.

A novel inclusion complex of oxybenzone with C-methylresorcin[4]arene deters skin permeation.

Oxybenzone (OXB), a very widely used sunscreen ingredient has the potential to block both UVA and UVB but can penetrate through skin. Studies have revealed its presence in the blood and urine of most humans, which may lead to long-term health effects. As the confined cavities of macrocycles can alter the physical and chemical properties of encapsulated guests, in this study, we investigated the formation of host-guest complexes between C-methylresorcin[4]arene and OXB. Combined experimental (NMR spectroscopy, UV/vis absorption, and fluorescence spectroscopy) and theoretical investigation confirmed the formation of a weak host-guest complex that had a 1 : 1 stoichiometry. Furthermore, skin permeation testing revealed that complexation by C-methylresorcin[4]arene significantly reduced the skin permeation of OXB which can potentially limit the harmful effects of this organic sunscreen.

Influence of skin furrows on tape stripping in characterizing the depth of skin penetration.

The stratum corneum (SC), the outermost layer of the skin and its major barrier for penetration, contains furrows of different depths on its surface. The presence of these furrows might lead to erroneous interpretation of the results in skin permeation studies using tape stripping, in which the material trapped in the furrows removed by the tapes representing different layers of the SC might be interpreted as material penetrating within these layers. The present objective was to investigate the effect of skin furrows on tape stripping results. Non-penetrating fluorescent materials were topically applied to split-thickness human and full-thickness porcine skin samples. Tape stripping was applied, and the tapes were assessed by fluorescence microscopy and quantitative analyses. The microscopy images were assessed visually to determine the presence of the applied material in the furrows. The penetration depth of the material was examined and the fluorescence content and pattern in each tape were analyzed. The results suggested that skin furrows could be important in the first 10 tapes, affecting the quantification of materials in the SC, particularly in permeation studies of materials with low penetration into the SC. Depending on the properties of the materials, skin rinsing could reduce the impact of furrows.

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.