title: Development of ciclopirox olamine topical formulations: evaluation of drug release, penetration and cutaneous retention.
abstract: With the aim of reducing system absorption and consequently, the side effects, and simultaneously select a penetration enhancing, three topical formulations with 0.5% ciclopirox olamine (CO) and 15% of propylene glycol (PG), ethoxydiglycol or oleic acid were developed and evaluated regarding the skin penetration and cutaneous retention of the drug using Franz diffusion cells. Release experiments were performed through synthetic membrane while dermatomed pig ear skin was used to evaluate CO skin penetration and skin retention. Retention studies were carried out applying tape stripping method and dosing CO in stratum corneum and in epidermis and dermis. A HPLC method was validated for quantifying CO. All formulations tested with synthetic membrane presented no retention of the drug. Permeation data suggested that there was no systemic absorption of ciclopirox olamine from the studied formulations, even when the skin penetration enhancers were applied. Higher concentrations of the drug were found in the stratum corneum (SC) and also in epidermis and dermis, for all of the developed formulations. The addition of enhancers improved the penetration and cutaneous retention of CO, and propylene glycol promoted higher concentrations in epidermis and dermis, probably because its cumulative effect on the skin and by an efficient solvent power.
authors.affiliation: Faculdade de Ciências Farmacêuticas da, Universidade de São Paulo , São Paulo, SP , Brazil.
authors.forename: Vanessa Alves
authors.initials: VA
authors.lastname: Pinheiro
authors.forename: Daniela
authors.initials: D
authors.lastname: Serikaku
authors.forename: Andre Rolim
authors.initials: AR
authors.lastname: Baby
authors.forename: Maria Valéria Robles
authors.initials: MV
authors.lastname: Velasco
authors.forename: Telma Mary
authors.initials: TM
authors.lastname: Kaneko
authors.forename: Vladi Olga
authors.initials: VO
authors.lastname: Consiglieri
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D000077768:Ciclopirox; D015194:Diffusion Chambers, Culture; D015195:Drug Design; D065546:Drug Liberation; D004355:Drug Stability; D066298:In Vitro Techniques; D010539:Permeability; D011728:Pyridones / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption; D063465:Skin Cream; D013552:Swine
chemical_list: D000935:Antifungal Agents; D011728:Pyridones; D000077768:Ciclopirox
keywords: Antifungal therapy; cutaneous retention; franz diffusion cell; lotion; penetration enhancers; skin permeation