title: Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport.
abstract: Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89±0.81μgcm-2h-1whereas the highest iontophoretic transport was 46.4±3.6μgcm-2h-1. These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations.
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n, 46113 Valencia, Spain; School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, 1 Rue Michel-Servet, 1211 Geneva, Switzerland. Electronic address: sergiodelrio@hotmail.es.
authors.forename: S
authors.initials: S
authors.lastname: Del Río-Sancho
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n, 46113 Valencia, Spain.
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, Avenida Seminario s/n, 46113 Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sebastián-Morelló
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n, 46113 Valencia, 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, Avenida Seminario s/n, 46113 Valencia, 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, Avenida Seminario s/n, 46113 Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Femenía-Font
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, 1 Rue Michel-Servet, 1211 Geneva, Switzerland.
authors.forename: Y N
authors.initials: YN
authors.lastname: Kalia
authors.affiliation: Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM) Universitat Politecnica de València, Universitat de València, Departamento de Farmacia y Tecnología Farmacéutica y Parasitologia, Universidad de Valencia, Valencia, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Merino
authors.affiliation: Instituto de Ciencias Biomédicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, Avenida Seminario s/n, 46113 Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: López-Castellano
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016503:Drug Delivery Systems; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007478:Iontophoresis; D008559:Memantine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D010539:Permeability; D012869:Skin Absorption; D013552:Swine
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008559:Memantine
keywords: Chemical penetration enhancers; Iontophoresis; Memantine; Occlusive-systems; Transdermal delivery