Combination strategies for enhancing transdermal absorption of sumatriptan through skin.
The aim of the present work was to characterize in vitro sumatriptan transdermal absorption through human skin and to investigate the effect of chemical enhancers and iontophoresis applied both individually and in combination. A secondary objective was to compare the results obtained with those in porcine skin under the same conditions, in order to characterize the relationship between the two skin models and validate the porcine model for further research use. Transdermal flux of sumatriptan was determined in different situations: (a) after pre-treatment of human skin with ethanol, Azone (1-dodecyl-azacycloheptan-2-one), polyethylene glycol 600 and R-(+)-limonene, (b) under iontophoresis application (0.25 and 0.50 mA/cm(2)) and (c) combining chemical pre-treatment and iontophoresis at 0.50 mA/cm(2) current density. All the strategies applied enhance sumatriptan transdermal absorption. A linear relationship between the fluxes in the two skin models in the different conditions assayed can be established. The combination of both strategies, Azone and iontophoresis, proved to be the most effective of the techniques for enhancing the transdermal absorption of sumatriptan. The flux obtained with porcine skin in vitro is approximately double that obtained in human skin.
Femenía-Font
A
A
Departamento de Fisiología, Farmacología y Toxicología, Facultad de Ciencias Experimentales y de la Salud, Universidad Cardenal Herrera-CEU, 46113 Moncada, Spain.
Balaguer-Fernández
C
C
Merino
V
V
López-Castellano
A
A
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D053138:Cyclohexenes / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods; D000077222:Limonene; D011092:Polyethylene Glycols / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D018170:Sumatriptan / Q000493:pharmacokinetics*; D034421:Sus scrofa; D013729:Terpenes / Q000494:pharmacology
D000277:Adjuvants, Pharmaceutic; D001381:Azepines; D053138:Cyclohexenes; D017366:Serotonin Receptor Agonists; D013729:Terpenes; C035229:laurocapram; D000431:Ethanol; D011092:Polyethylene Glycols; D018170:Sumatriptan; D000077222:Limonene