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.

Engineering and Development of Chitosan-Based Nanocoatings for Ocular Contact Lenses

“…Chitosan has previously been utilised as a release modulator and PE for an array of biological membranes including buccal tissue (Duttagupta, Jadhav et al 2015, Kontogiannidou, Andreadis et al 2017, intestinal tissue (Chougule, Patel et al 2014, Maher, Mrsny et al 2016, Ates, Kaynak et al 2016, nasal cavity (Benediktsdottir, Baldursson et al 2014, Giuliani, Balducci et al 2018. Chitosan has also been scrutinised in the ocular drug delivery due to its permeation enhancement properties; with drugs such as ofloxacin (Di Colo, Burgalassi et al 2004), triamcinolone acetonide (Raval, Khunt et al 2018) and timolol maleate (Rodriguez, Antonio Vazquez et al 2017).…”

Comparative bioavailability study following a single dose intravenous and buccal administration of remdesivir in rabbits

“…When triclosan complexed with SBECD or HPBCD (2-hydroxypropyl-beta-cyclodextrin, a neutral CD derivative) no difference was found in adhesion to porcine buccal adhesion ( Sigurdsson et al, 2002 ). In a similar study, the authors found only a slightly higher transport of SBECD/roprinolone compared to HPBCD/roprinolone across porcine buccal epithelium: 28 and 24% improvement compared to buffer only ( Kontogiannidou et al, 2017 ).…”

In Vitro and Ex Vivo Evaluation of Tablets Containing Piroxicam-Cyclodextrin Complexes for Buccal Delivery

“…Detachment of the epithelium from underlying stroma and mild disorganization at basal membrane are illustrated in the micrographs of Figure 7c and Figure 8c for Me-β-CD, with only rare acantholysis and inter-epithelial gaps in tablet form. In Figure 7d and Figure 8d, desquamation of superficial keratinocytes and mild disorganization of collagen beneath basal membrane could be identified for HP-β-CD [3,8,29]. The loss of the superficial cell layers might imply interactions between the CDs and the epithelial lipids given that CDs can induce lipid solubilization [30].…”

“…Buccal mucosa is an alternative site for the delivery of drugs into the systemic circulation [1]. The drug administered through the buccal mucosa enters to the systemic circulation directly via the jugular vein [2], minimizing the first-pass hepatic metabolism, and avoiding the adverse gastro-intestinal tract [3]. Buccal delivery of active pharmaceutical ingredients (APIs) is an alternative, non-invasive route of administration that provides beneficial health effects.…”