Drug release kinetics and fronts movement studies from methyl methacrylate (MMA) copolymer matrix tablets:: effect of copolymer type and matrix porosity

Several methyl methacrylate (MMA) copolymers have recently been proposed as an alternative for the formulation of controlled-release matrix tablets. Copolymers were synthesised by free radical copolymerisation of methyl methacrylate with starch or cellulose derivatives and were alternatively dried by oven or freeze-drying techniques. Both the chemical composition and the drying technique were demonstrated to have a considerable influence on the physical properties of the copolymers. The present investigation was focused on the elucidation of the drug release mechanism from MMA copolymer matrices, using anhydrous theophylline as model drug. Drug release experiments were performed from free tablets. Radial drug release and fronts movement were also evaluated using special devices consisting of two Plexiglasso discs joined by means of four stainless steel screws. Mathematical analysis of release data was performed using Higuchi, Korsmeyer and Peppas equations and fronts movement was investigated using a colorimetric technique. The drug release rate and the relative positions of the fronts were studied as functions of the type of copolymer and the initial porosity of the tablets. Drug release was controlled mainly by diffusion and the release rate was found to be affected by the drying method and related to the area exposed to the dissolution medium. Three distinct fronts (water uptake, complete wetting, erosion) were observed during the release process and the dynamics of fronts movement confirmed the diffusional mechanism. (C) 2003 Elsevier B.V. All rights reserved.