title: Ex vivo buccal drug delivery of ropinirole hydrochloride in the presence of permeation enhancers: the effect of charge.
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.
authors.affiliation: a Laboratory of Pharmaceutical Technology , Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki , Thessaloniki , Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Kontogiannidou
authors.affiliation: b Department of Oral Medicine/Pathology , School of Dentistry, Aristotle University of Thessaloniki , Thessaloniki , Greece.
authors.forename: Dimitrios A
authors.initials: DA
authors.lastname: Andreadis
authors.affiliation: c Laboratory of Organic Chemistry , Department of Chemistry, Aristotle University of Thessaloniki , Thessaloniki , Greece.
authors.forename: Alexandros L
authors.initials: AL
authors.lastname: Zografos
authors.affiliation: d School of Medicine, Pharmacy and Health, Durham University , Stockton on Tees , UK.
authors.forename: Hamde
authors.initials: H
authors.lastname: Nazar
authors.affiliation: e Laboratory of Pharmaceutical Technology , Department of Pharmaceutical Sciences, University of Patras , Patras , Greece , and.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Klepetsanis
authors.affiliation: f School of Pharmacy and Biomedical Sciences, University of Portsmouth , Portsmouth , UK.
authors.forename: Susanna M
authors.initials: SM
authors.lastname: van der Merwe
authors.affiliation: a Laboratory of Pharmaceutical Technology , Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki , Thessaloniki , Greece.
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Fatouros
mesh_terms: D000818:Animals; D048271:Chitosan; D016503:Drug Delivery Systems; D007211:Indoles / Q000008:administration & dosage*; D009061:Mouth Mucosa; D010539:Permeability; D013552:Swine; D047392:beta-Cyclodextrins
chemical_list: D007211:Indoles; C118071:N-trimethyl chitosan chloride; D047392:beta-Cyclodextrins; C046649:ropinirole; D048271:Chitosan
keywords: Buccal delivery; Parkinson’s disease; permeation enhancers; ropinirole hydrochloride