title: Skin permeation of econazole nitrate formulated in an enhanced hydrophilic multiple emulsion.
abstract: Local delivery of imidazolic antifungals is limited by its extreme lipophilicity. Multiple emulsions (ME) are a potential vehicle to enhance the delivery of econazole nitrate (ECN), an antifungal targeted to deep-seated epidermal yeast infections. An 1% ECN hydrophilic ME was compared with a commercial formulation in terms of rheology, droplet size and in vitro antifungal activity against Candida species. Comparative in vitro drug release, human skin permeation and drug retention were investigated using vertical diffusion cells. Rheology demonstrated a pseudoplastic shear thinning with thixotropy facilitating skin residence. No significant aggregation or droplet size variations were observed during a 6-month stability storage. Both formulations exhibited similar release levels achieving asymptotic values in 5 h. ECN skin permeation levels from the multiple emulsion resulted to be significantly higher than those of the commercial formulation, attributable to differences in formulation polarity and excipients composition. Conversely, similar drug accumulation levels in skin were obtained (40-130 ppm). These concentrations resulted to be comparable with obtained MIC values (2-78 ppm), confirming the in vitro antimicrobial efficacy of both formulations. A similar skin retention and a higher permeation rate over the existing formulations is considered an improved approach to target the drug to deep epidermis.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Suñer-Carbó
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Boix-Montañés
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
authors.forename: Lyda
authors.initials: L
authors.lastname: Halbaut-Bellowa
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
authors.forename: Nelvis
authors.initials: N
authors.lastname: Velázquez-Carralero
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
authors.forename: Joanna
authors.initials: J
authors.lastname: Zamarbide-Ledesma
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Bozal-de-Febrer
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Calpena-Campmany
mesh_terms: D000279:Administration, Cutaneous; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002175:Candida / Q000187:drug effects; D015194:Diffusion Chambers, Culture; D004339:Drug Compounding; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D004464:Econazole / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004655:Emulsions; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D012867:Skin / Q000378:metabolism* / Q000382:microbiology; D012869:Skin Absorption
chemical_list: D000935:Antifungal Agents; D004655:Emulsions; D004464:Econazole
keywords: W/O/W multiple emulsion; antifungal delivery; candidiasis; drug release; skin permeation