Buccal Delivery of Methimazole as an Alternative Means for Improvement of Drug Bioavailability: Permeation Studies and Matrix System Design

Viviana      De Caro; Giulia      Giandalia; Maria      Gabriella Siragusa; Libero      Italo Giannola

doi:10.2174/138161212803307563

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.

Keywords: Methimazole, hyperthyroidism, transbuccal permeation, porcine buccal mucosa, Eudragit ®RS 100, buccal tablets, drug delivery buffer solution, saliva, mucoadhesive.