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Simultaneous controlled iontophoretic delivery of pramipexole and rasagiline in vitro and in vivo: Transdermal polypharmacy to treat Parkinson's disease.
Journal article

Simultaneous controlled iontophoretic delivery of pramipexole and rasagiline in vitro and in vivo: Transdermal polypharmacy to treat Parkinson's disease.

  • Kalaria DR School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, CMU, 1 rue Michel Servet, 1211 Geneva, Switzerland.
  • Singhal M School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, CMU, 1 rue Michel Servet, 1211 Geneva, Switzerland.
  • Patravale V Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400019, India.
  • Merino V Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM) Universitat Politecnica de València, Universitat de València, Spain; Departamento de Farmacia y Tecnología Farmacéutica y Parasitología, Faculty of Pharmacy, University of Valencia, Avda.Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
  • Kalia YN School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, CMU, 1 rue Michel Servet, 1211 Geneva, Switzerland. Electronic address: yogi.kalia@unige.ch.
  • 2018-02-26
Published in:
  • European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. - 2018
Dopamine agonist
Iontophoresis
MAO-B inhibitor
Patient compliance
Transdermal
Administration, Cutaneous
Animals
Benzothiazoles
Chemistry, Pharmaceutical
Electroosmosis
Humans
Indans
Iontophoresis
Male
Parkinson Disease
Permeability
Polypharmacy
Pramipexole
Rats
Rats, Wistar
Skin
Skin Absorption
Swine
English Effective treatment of Parkinson's disease (PD) involves administration of therapeutic agents with complementary mechanisms of action in order to replenish, sustain or substitute endogenous dopamine. The objective of this study was to investigate anodal co-iontophoresis of pramipexole (PRAM; dopamine agonist) and rasagiline (RAS; MAO-B inhibitor) in vitro and in vivo. Passive permeation of PRAM and RAS (20 mM each) across porcine skin after 6 h was 15.7 ± 1.9 and 16.0 ± 2.9 µg/cm2, respectively. Co-iontophoresis at 0.15, 0.3 and 0.5 mA/cm2 resulted in statistically significant increases in delivery of PRAM and RAS; at 0.5 mA/cm2, cumulative permeation of PRAM and RAS was 613.5 ± 114.6 and 441.1 ± 169.2 µg/cm2, respectively - corresponding to 38- and 27-fold increases over passive diffusion. Electromigration was the dominant mechanism for both molecules (>80%) and there was no effect on convective solvent flow. Statistically equivalent delivery was observed with human skin. The co-iontophoretic system showed high delivery efficiency with 29% and 35% of the applied amounts of PRAM and RAS being delivered. Preliminary pharmacokinetics studies in rats confirmed that the input rate in vivo was such that therapeutic amounts of the two drugs could be co-administered to humans by transdermal iontophoresis using reasonably sized patches and moderate current densities.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/232678
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