Comparative studies on the effects of water, ethanol and water/ethanol mixtures on chemical partitioning into porcine stratum corneum and silastic membrane

Abstract

The effects of water and ethanol vehicles on stratum corneum and silastic membrane partitioning of 11 industrial and agricultural compounds were studied to aid in characterizing and assessing risk from skin exposure. Zero percent, 50% and 100% aqueous ethanol solutions were used as solvents for 14 C labeled phenol, 4-nitrophenol, pentachlorophenol, dimethyl parathion, parathion, chloropyrifos, fenthion, triazine, atrazine, simazine and propazine. Compound partitioning between the solvents and porcine stratum corneum/silastic membrane were estimated. Stratum corneum was exposed to aqueous ethanol ranging from 0% to 100% v/v ethanol in 20% increments and Fourier transform infrared spectroscopy (FT-IR) was used to obtain an index of lipid disorder. Gravimetry and FT-IR were used to demonstrate lipid extraction in aqueous ethanol solutions.Partitioning patterns in silastic membranes resembled those in stratum corneum and were correlated with octanol/water partitioning. Partitioning was highest in water and was higher from 50% ethanol than from 100% ethanol, except for parathion, 4-nitrophenol, atrazine and propazine. Correlation existed between molecular weight and partitioning in water, but not in ethanol and ethanol/water mixtures. Lipid order, as reflected in FT-IR spectra, was not altered. These studies suggest that stratum corneum partitioning of the compounds tested is primarily determined by relative compound solubility between the stratum corneum lipids and the donor solvent. Linear relationships existed between octanol/water partitioning and stratum corneum partitioning.Partitioning was also correlated with molecular weight in water solvent systems, but not in ethanol and ethanol/water mixtures. Ethanol and ethanol/water mixtures altered the stratum corneum through lipid extraction, rather than through disruption of lipid order.

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

“…4,5) Regarding the pretreatment effects of EtOH, however, little was found on skin permeation of drugs compared with simultaneous application of EtOH and drugs. Furthermore, few reports were found on the relation between the skin permeation of drugs and their lipophilicity and/or molecular weight after treatment with EtOH.…”

“…[1][2][3] It has been proposed that the mechanisms of EtOH effects on the stratum corneum are extraction of lipids, increases in lipid fluidity, enhancement of drug solubility in stratum corneum lipids, changes in skin hydration, effects on the putative pore pathway, alterations in keratinized proteins, and effects on solvent drugs. 4,5) Regarding the pretreatment effects of EtOH, however, little was found on skin permeation of drugs compared with simultaneous application of EtOH and drugs. Furthermore, few reports were found on the relation between the skin permeation of drugs and their lipophilicity and/or molecular weight after treatment with EtOH.…”

Modelling the effect of mixture components on permeation through skin

“…Lipophilicity of a compound dictates the partitioning behavior into corneocytes. It can be postulated that hydrophilic compounds tend to partition into the corneocyte proteins while more lipophilic compounds into the SC lipids Van der Merwe and Riviere, 2005). There is evidence in the literature which is also supported by quantitative structure-activity relationship (QSAR) studies (Ghafourian and Fooladi, 2001) which indicates the higher partitioning of more lipophilic compounds containing fewer heteroatoms into the lipid domain of SC, while partitioning to protein domain is less sensitive to the size and number of heteroatoms of penetrants.…”

“…From the above, given also the almost unlimited possible combinations of solvent mixtures and permeants, it can be assumed that the accurate prediction of diffusion and partition from permeant and solvent chemical data is uncertain (Van der Merwe and Riviere, 2005). On the other hand large sets of empirical data provide us with valuable certainty in the process of identifying characteristics of permeant and vehicle systems that have consistent effects across a wide range of experimental conditions.…”

Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations

“…Finally, ethanol is a highly volatile constituent that might extract some of the lipid fraction from within the SC, with the consequence of improved drug flux through the skin when used at high concentrations for prolonged times. 36 In other words, ethosomes would disrupt the lipophilic barrier of the skin. This barrier depends on the molecular weight and distribution coefficient rather than molecular size of permeants.…”