Passive and iontophoretic transport of pramipexole dihydrochloride across human skin microchannels created by microneedles in vitro

Skin microchannels (MCs) created by microneedles (MNs) provide a promising route for enhancing transdermal drug delivery. This study investigated passive and iontophoretic transport of pramipexole dihydrochloride (PXCl) across skin MCs created by polymer MN patches made of 1:2 polymethyl-vinyl-ether-co-maleic acid (PMVEMA) to polyvinyl alcohol (PVA) ratio. Permeation studies were performed in vitro using excised human skin under the conditions of (i) "poke-and-patch" and "poke-and-release" delivery approaches with varying concentration of PXCl in the formulations, (ii) drug-loaded dissolving MN (DMN) and hydrogel-forming MN (HGMN) type patches and (iii) combination of MNs and iontophoresis. The results showed that DMN patch greatly enhanced transdermal delivery of PXCl for both "poke-and-patch" and "poke-and-release" approaches as compared with the conventional delivery method. PXCl flux mainly resulted from the contribution of MC pathway created in skin and increased with increasing drug amounts in the formulations. Compared to DMN patch, HGMN patch provided more linear sustained drug delivery over 72 h. Electromigration was the main mechanism of PXCl iontophoresis through MCs and flux enhancement was found to be larger for HGMN patch than DMN patch. These results demonstrated the potential application of MN patches individually or combined with iontophoresis as an alternative method for PXCl administration.