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 (TI'S) 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 ITS 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 expefiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89 +/- 0.81 mu g cm(-2) h(-1) whereas the highest iontophoretic transport was 46.4 +/- 3.6 mu g cm(-2) h(-1). These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations. (C) 2016 Elsevier B.V. All rights reserved.