Bioadhesive Buccal Discs of Fluvastatin Sodium

Abstract

Purpose: The aim of this work was to formulate buccoadhesive discs of fluvastatin sodium (FVS) to be applied to the buccal mucosa, releasing the drug in a unidirectional manner, in order to improve the bioavailability of the drug and lower the dose-dependent adverse events. Methods: The bioadhesive discs were prepared by direct compression using several bioadhesive polymers such as carbopol 934P, sodium carboxymethyl cellulose, sodium alginate, hydroxypropylmethyl cellulose, and guar gum. Ethyl cellulose was applied as the backing layer to achieve unidirectional release towards the mucosa. To improve drug release, microcrystalline cellulose or polyethylene glycol 6000 (PEG 6000) were added. Different permeation enhancers such as bile salts, surfactants, fatty acids, and dimethyl sulfoxide were tested to improve the permeability across buccal mucosa. Chicken pouch membrane was the used model membrane in drug permeation and bioadhesion strength and time studies. In-vivo relative bioavailability study was performed for the selected formulation on six healthy human volunteers using a commercial peroral product (Lescol®, Novartis) as a reference formulation. Plasma concentrations of fluvastatin were determined by liquid chromatography-mass spectrometry (LC-MS/MS).