Gel-matrixsystems exhibiting bimodal controlled release for oral drug delivery

Abstract

Certain types of hydroxypropyl methylcellulose ethers, when admixed with a therapeutic agent and compressed into a solid dosage form, are found to display a bimodal drug release profile. The bimodal profile is characterized by a rapid initial release of drug, followed by a constant rate of release, and then a second mode of fast drug release at the terminal phase. Release profiles can be selectively modified by varying the viscosity, concentration, and the combination of methylcellulose polymers. The mechanism of release appears to involve initial surface erosion, polymer gelation, a steady-state counter-current permeation of water and dissolved drug across the gel layer, dissolution of gel from the outer surface, and subsequent disintegration of the gel. A bimodal oral controlled release delivery system which produces an increased rate of drug release in the latter phases of dissolution, may offer some advantages over constant zero-order release systems for maintaining uniform drug levels in the body. Bimodal release profiles were obtained for aspirin, ibuprofen, adinazolam, flurbiprofen, and other investigational drugs.