Ex vivo buccal drug delivery of ropinirole hydrochloride in the presence of permeation enhancers: the effect of charge

Eleni Kontogiannidou, Dimitrios Andreadis, Alexandros Zografos, Hamde Nazar, Pavlos Klepetsanis, Marisa Van Der Merwe, Dimitrios G. Fatouros

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Abstract

In the current study, the ex vivo permeation of ropinirole hydrochloride (RH) across porcine buccal mucosa in the presence of three permeation enhancers, namely N-trimethyl chitosan (TMC) (positively charged) a chitosan derivative, sulfobutyl ether-β-cyclodextrin (SBE-β-CD) (negatively charged) and hydroxypropyl-β-cyclodextrin (HP-β-CD) (neutral), was investigated. Buccal permeation studies were conducted using Franz diffusion cells. Cumulative amounts of RH were plotted versus time. The presence of the permeation enhancers significantly increased the transport of the drug across the porcine buccal epithelium compared to its plain congener (RH solution). The rank order effect of the permeation enhancers for the transport of RH across buccal epithelium was TMC ≥ SBE-β-CD > HP-β-CD > RH solution. The presence of TMC increased 1.34-fold the transport of RH across buccal epithelium, whereas an increase of 1.23- and 1.28-fold was reported in the presence of HP-β-CD and SBE-β-CD, respectively. Infrared spectroscopy (IR) was employed to investigate the interaction of permeation enhancers with the epithelial lipids of porcine buccal mucosa corroborating the permeation results. Finally, light microscopy was performed to assess the histological changes in the porcine epithelium. Formation of vacuoles, spongiosis and acantholysis linear detachment and destruction of the epithelium resulted from the presence of the permeation enhancers. The data suggest that all enhancers tested, and particularly TMC, increase the transport of RH across buccal epithelium.
Original languageEnglish
Pages (from-to)1017-1021
JournalPharmaceutical Development and Technology
Volume22
Issue number8
Early online date21 Jan 2016
DOIs
Publication statusPublished - Aug 2017

Keywords

  • Buccal delivery
  • Parkinson’s disease
  • permeation enhancers
  • ropinirole hydrochloride

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