Enhancing effect of alpha-hydroxyacids on "in vitro" permeation across the human skin of compounds with different lipophilicity.
The percutaneous penetration-enhancing effects of glycolic acid, lactic acid and sodium lauryl sulphate through the human epidermis was investigated using 5-fluorouracil as a hydrophilic model permeant and three compounds belonging to the phenylalcohols: 2-phenyl-ethanol, 4-phenyl-butanol and 5-phenyl-pentanol. The lipophilicity values of the compounds ranged from log Poct -0.95 to 2.89. The effect of the enhancer concentration was also studied. Skin pretreatment with aqueous solutions of the three enhancers did not increase the permeability coefficient of the most lipophilic compound (log Poct = 2.89). For the other compounds assayed, the increase in the permeability coefficients depended on the concentration used in skin pretreatment, and on the lipophilicity of the compounds tested-and was always greater for the most hydrophilic compound (5-fluorouracil), for which lactic acid exerted a greater enhancer effect than glycolic acid or sodium lauryl sulphate. Primary irritation testing of the three enhancers was also carried out at the two concentrations used in skin pretreatment for diffusional experiments (1% and 5%, w/w). The least irritant capacity corresponded to lactic acid; consequently, this alpha-hydroxyacid could be proposed as a percutaneous penetration enhancer for hydrophilic molecules that are of interest for transdermal administration.
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Avd. Vicente Andrés Estellés, s/n 46100 Burjassot, Valencia, Spain.
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Herráez-Domínguez
D000328:Adult; D000438:Alcohols / Q000493:pharmacokinetics*; D000440:Butanols / Q000493:pharmacokinetics; D004817:Epidermis / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006016:Glycolates / Q000494:pharmacology; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000494:pharmacology; D000439:Pentanols / Q000493:pharmacokinetics; D010539:Permeability; D010626:Phenylethyl Alcohol / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology
D000438:Alcohols; D000440:Butanols; D006016:Glycolates; D006880:Hydroxy Acids; D000439:Pentanols; C031149:glycolic acid; D019344:Lactic Acid; D012967:Sodium Dodecyl Sulfate; C511376:5-phenylpentanol; D010626:Phenylethyl Alcohol; C511375:4-phenylbutanol; D005472:Fluorouracil