4.7 Article

Current profile controlled transdermal delivery of pramipexole from an iontophoretic patch system in vitro and in vivo

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ELSEVIER
DOI: 10.1016/j.ejpb.2021.06.010

Keywords

Iontophoresis; Transdermal; Dopamine agonist; Multi-phasic current profile; Iontophoretic patch; Parkinson's disease

Funding

  1. Swiss Federal Commission for Scholarships for Foreign Students
  2. University of Geneva

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The study demonstrated that in vitro experiments using constant and complex multi-phasic current profiles from an iontophoretic patch system showed that single compartment systems and two-compartment iontophoretic patches with NaCl added were relatively effective in delivering pramipexole.
The objective was to evaluate the transdermal iontophoretic delivery of pramipexole using constant and complex multi-phasic current profiles from an iontophoretic patch system in vitro and in vivo. Preliminary in vitro experiments were performed to optimize iontophoretic patch design and configuration. Single compartment systems containing only pramipexole dihydrochloride, and designed to maximize delivery efficiency, suffered from an insufficiency of chloride ions with anodal electrochemistry passing from an Ag/AgCl couple to an Ag dissolution electrode. Addition of NaCl to provide more chloride ions decreased pramipexole delivery efficiency due to competition between pramipexole and sodium cations. A two-compartment iontophoretic patch where the drug reservoir was separated from the anodal compartment, which now included NaCl, was shown to be a good compromise since it ensured Ag/AgCl electrochemistry at the anode and an acceptable delivery efficiency. In vivo studies using this iontophoretic patch demonstrated that the plasma concentration of pramipexole closely followed the variation of the applied continuous and multi-phasic current profiles and underlined the control provided by iontophoresis and its unique ability to rapidly change drug input rates. The applied current density and duration of current application were also shown to modulate pramipexole delivery to the brain and CSF.

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