Title:Buccal Delivery of Methimazole as an Alternative Means for Improvement of Drug Bioavailability: Permeation Studies and Matrix System Design
Volume: 18
Issue: 34
Author(s): Viviana De Caro, Giulia Giandalia, Maria Gabriella Siragusa and Libero Italo Giannola
Affiliation:
Keywords:
Methimazole, hyperthyroidism, transbuccal permeation, porcine buccal mucosa, Eudragit
®RS 100, buccal tablets, drug delivery buffer solution, saliva, mucoadhesive.
Abstract: The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal
mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low
permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal
mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor
phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (Js = 0.068
mg cm-2 h-1 and Kp = 0.065 cm h-1).
Matrix tablets, suitable for administration on buccal mucosa, were then designed and prepared by direct compression of MMI loaded matrices
(70% w/w) using Eudragit® RS 100 as a matrixing, low permeable, pH-independent, mucoadhesive and insoluble agent.
The matrix tablets were evaluated in vitro for dissolution; however, the drug was discharged too rapidly from tablets. To obtain drug release
rate suitable to maintain constant drug levels in the central compartment the tablets were coated with lipophilic material (glycerol
tristearate). In ex vivo permeation experiments, therapeutically MMI plasma levels were obtained when matrix tablets were coated with
0.10 mm thick lipophilic coating film. Coated tablets placed on buccal porcine mucosa provide optimal drug release rate.
Coated buccal matrix tablets may represent a potential alternative dosage form for systemic delivery of MMI in hyperthyroidism management.
