Oil based nanocarrier system for transdermal delivery of ropinirole: a mechanistic, pharmacokinetic and biochemical investigation

Int J Pharm. 2012 Jan 17;422(1-2):436-44. doi: 10.1016/j.ijpharm.2011.10.039. Epub 2011 Oct 25.

Abstract

Ropinirole, a recent introduction in the clinical treatment of Parkinson's disease, suffers with the problems of low oral bioavailability and frequent dosing. An effective transdermal nano-emulsion drug delivery system can however resolve these issues effectively with greater therapeutic benefits and clinical significance. Therefore, the present work focuses precisely on pharmacokinetic, biochemical and mechanistic assessment of transdermal nanoemulsion gel in rats induced with Parkinson lesioned brain by 6-OHDA. DSC and FT-IR studies showed that NEG affects the normal lipid packing of stratum corneum to enhance the drug permeation. Study of pharmacokinetic parameters (AUC, C(max), and T(max)) revealed a greater and more extended release of ropinirole from nanoemulsion gel compared to that from a conventional gel (RPG) and oral marketed tablet (Ropitor). The AUC(0→∞) for RPCNG and RPTNG was found to be 928.07 ± 206.5 and 1055.99 ± 251.7 ngh/mL, respectively in comparison to 137.25 ± 31.3 and 467.15 ± 106.1 ngh/mL for RPG and oral tablet, respectively. The relative bioavailability of ropinirole has been enhanced more than two fold by RPTNG. Furthermore, antiparkinson activity was evaluated in terms of estimating the level of thiobarbituric acid reactive substances, glutathione antioxidant enzymes and catalase in lesioned brain of rats. Formulations were also found to be non-toxic and non-irritant by histological investigations.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Animals
  • Antiparkinson Agents / administration & dosage
  • Antiparkinson Agents / blood
  • Antiparkinson Agents / chemistry
  • Antiparkinson Agents / pharmacokinetics*
  • Biological Availability
  • Brain / drug effects
  • Brain / metabolism
  • Calorimetry, Differential Scanning
  • Catalase / metabolism
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Dihydroxyphenylalanine / analogs & derivatives
  • Disease Models, Animal
  • Drug Carriers*
  • Drug Compounding
  • Emulsions
  • Gels
  • Glutathione / metabolism
  • Indoles / administration & dosage
  • Indoles / blood
  • Indoles / chemistry
  • Indoles / pharmacokinetics*
  • Male
  • Nanoparticles*
  • Nanotechnology*
  • Oils / chemistry*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism
  • Rats
  • Rats, Wistar
  • Skin Absorption
  • Spectroscopy, Fourier Transform Infrared
  • Tablets
  • Technology, Pharmaceutical / methods*
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Antiparkinson Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Emulsions
  • Gels
  • Indoles
  • Oils
  • Tablets
  • Thiobarbituric Acid Reactive Substances
  • ropinirole
  • 6-hydroxydopa
  • Dihydroxyphenylalanine
  • Catalase
  • Glutathione