Bimodal Release of Theophylline from “Seed–Matrix” Beads Made of Acrylic Polymers

Abstract

The purpose of this research was to design a “seed–matrix” structure for an in vitro bimodal theophylline release profile and to investigate the mechanism and kinetics of drug release as well as the influence of various factors on the properties of the theophylline-containing microspheres. “Seed” microspheres with high theophylline content were prepared from Eudragit® L100 and Eudragit S100, copolymers of methyl methacrylate and methacrylic acid, by the solvent removal process. The seed–matrix beads were subsequently prepared by incorporation of the seed microspheres into Eudragit RL100, a copolymer of acrylic and methacrylic acid esters with a low content of quaternary ammonium group. Increasing the size of encapsulated drug particles and the rate of agitation during the preparation, or decreasing the amount of surfactants led to an increase in the size of the microspheres produced. Scanning electron microscopy revealed porous morphology of the microspheres. The release rate of theophylline was enhanced as the content of methacrylic acid in the copolymer increased and the size of the microspheres decreased. The kinetics of drug release from the microspheres was controlled by swelling at the early stage and by diffusion in the later stage. The drug was released from the matrix of the seed–matrix beads at pH 1.2 and from both the matrix and the seeds at pH 6.8. A bimodal release profile of theophylline was obtained from the seed–matrix beads made of acrylic polymers.