title: Development of antimigraine transdermal delivery systems of pizotifen malate.
abstract: The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate.
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, 46113 Moncada, Spain. Electronic address: cesar.serna@hotmail.es.
authors.forename: C E
authors.initials: CE
authors.lastname: Serna-Jiménez
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, 46113 Moncada, Spain.
authors.forename: S
authors.initials: S
authors.lastname: del Rio-Sancho
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, 46113 Moncada, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Calatayud-Pascual
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, 46113 Moncada, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Balaguer-Fernández
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, 46113 Moncada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Femenía-Font
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, 46113 Moncada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: López-Castellano
authors.affiliation: Instituto de Reconocimiento Molecular y Desarrollo Tecnológico, Centro Mixto Universidad Politécnica de Valencia-Universidad de Valencia, Spain; Departamento de Farmacia y Tecnología Farmacéutica, Universidad de Valencia, Valencia, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Merino
mesh_terms: D000279:Administration, Cutaneous; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D001381:Azepines / Q000737:chemistry; D003511:Cyclohexanols / Q000737:chemistry; D053138:Cyclohexenes / Q000737:chemistry; D016503:Drug Delivery Systems; D000431:Ethanol / Q000737:chemistry; D000077591:Eucalyptol; D005227:Fatty Acids / Q000737:chemistry; D066298:In Vitro Techniques; D007478:Iontophoresis; D000077222:Limonene; D008881:Migraine Disorders / Q000188:drug therapy; D039821:Monoterpenes / Q000737:chemistry; D010918:Pizotyline / Q000008:administration & dosage* / Q000737:chemistry; D012869:Skin Absorption; D013552:Swine; D013729:Terpenes / Q000737:chemistry
chemical_list: D018712:Analgesics, Non-Narcotic; D001381:Azepines; D003511:Cyclohexanols; D053138:Cyclohexenes; D005227:Fatty Acids; D039821:Monoterpenes; D013729:Terpenes; D010918:Pizotyline; C035229:laurocapram; D000431:Ethanol; D000077222:Limonene; D000077591:Eucalyptol
keywords: Chemical enhancers; Iontophoresis; Migraine; Pizotifen; Pizotifen malate (Pubchem CID: 168993); TDS; Transdermal