Chitosan as a pore former in coated beads for colon specific drug delivery of 5-ASA

Abstract

A multiparticulate product for colon-specific delivery of a small molecule drug has been developed and characterized. Microcrystalline cellulose core beads containing 5-aminosalicylic acid produced by extrusion-spheronization were coated with chitosan and Aquacoat(®) ECD mixtures according to a factorial design. Coated beads were characterized in terms of drug release, shape, and friability. The optimum formulation was enteric coated and exposed to media simulating conditions in the stomach, small intestine, and colon. Release studies in simulated intestinal fluid revealed that the drug release rate from the coated beads, which were spherical and rugged, depended on the level of chitosan in the coat and the coat thickness. Enlarged pores observed on the surface of the coated beads exposed to the medium containing rat cecal and colonic enzymes are believed to have caused a significant enhancement of the drug release rate compared to the control exposed only to simulated gastric and intestinal fluids. The release mechanisms involved polymer relaxation and dissolved drug diffusion for simulated intestinal fluid and simulated colonic fluid, respectively. From the facilitated drug release in a colonic environment and the inhibition of drug release under gastric and intestinal conditions, it can be concluded that this multiparticulate system demonstrates the potential for colon-specific drug delivery.