Formulation and in vitro/in vivo evaluation of levodopa transdermal delivery systems

Int J Pharm. 2013 Nov 18;456(2):432-6. doi: 10.1016/j.ijpharm.2013.08.044. Epub 2013 Sep 2.

Abstract

This study aims to investigate the feasibility of Levodopa transdermal delivery systems (TDSs). Levodopa TDSs were formulated using various vehicles and permeation enhancers, and in vitro permeation and in vivo pharmacokinetic studies were carried out. In the in vitro study, ester-type vehicles showed relatively high enhancing effects; propylene glycol monocaprylate and propylene glycol monolaurate showed the highest permeation fluxes from both solution and pressure sensitive adhesive (PSA) TDS formulations. Lag time was dramatically shortened with PSA TDS formulations as compared with solution formulations. In the in vivo study, the addition of fatty acids increased blood drug concentrations regardless of the kind or concentration of fatty acid; the AUCinf increased up to 8.7 times as compared with propylene glycol (PG) alone. PSA TDS containing 10% linoleic acid exhibited prolonged Tmax as compared with oral form. Total clearance of L-dopa from PSA TDSs was significantly lower than from oral form (up to 86.8 times). Especially, PSA TDS containing 10% linoleic acid (LOA) revealed 76.2 fold higher AUCinf than oral administration. Based on our results, the L-dopa PSA TDS containing PG with 10% LOA could be used as a good adjuvant therapy for Parkinson's disease patients who experience symptom fluctuation by L-dopa oral administration.

Keywords: AAAD; C-dopa; EA; EDTANa(2); HAS; IPA; IPM; L-dopa; LBF1944; LBF2609; Levodopa; OA; PD; PEG400; PG; PGL; PGMC; PGML; PSA; Parkinson's disease; Permeation; Pharmacokinetics; TDS; Transdermal delivery system; carbidopa; disodium ethylenediamine tetraacetic acid; ethyl alcohol; heptanesulphonate; isopropyl alcohol; isopropyl myristate; l-aromatic amino acid decarboxylase; levodopa; oleoyl macrogol-6 glyceride; oleyl alcohol; polyethylene glycol 400; pressure sensitive adhesive; propylene glycol; propylene glycol laurate; propylene glycol monocaprylate; propylene glycol monolaurate; propylene glycol-8 glyceryl linoleate; transdermal delivery systems.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Chemistry, Pharmaceutical
  • Drug Delivery Systems / methods*
  • Drug Evaluation, Preclinical / methods
  • Humans
  • Levodopa / administration & dosage*
  • Levodopa / blood
  • Levodopa / chemistry*
  • Male
  • Mice
  • Mice, Hairless
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Skin Absorption / drug effects*
  • Skin Absorption / physiology

Substances

  • Levodopa