New interpenetrating polymeric network (IPN) hydrogels based on chitosan (C), poly(N-vinyl pyrrolidone) (PVP) and poly(acrylic acid) (PAAc), crosslinked with glutaraldchyde (G) and N,N'-methylenebisacrylamide (MBA), were prepared and investigated for potential gastrointestinal drug delivery vehicles utilizing a model drug, amoxicillin. IPN hydrogels were synthesized by simultaneous polymerization/crosslinking of acrylic acid monomer in the presence of another polymer (C) and crosslinker (G, MBA). Three different concentrations of glutaraldehyde were used (0.5, 1.0 and 2.0 w/w) to control the overall porosity of the hydrogels, named C-P-AAc/0.5, C-P-AAc/1.0 and C-P-AAc/2.0, respectively. Spectroscopic and thermal analyses such as Fourier transform infrared spectroscopy, thermogravimetric analysis and thermornechanical analysis were performed for IPN characterization. Equilibrium swelling studies were conducted for pH and temperature response behavior. Swelling studies were also carried out in simulated gastric fluid of pH = 1.1 and simulated intestinal fluid of pH = 7.4 to investigate possible site-specific drug delivery. It was found that the release behavior of the drug from these IPN hydrogels was dependent on the pH of the medium and the proportion of crosslinker in the IPN. It was observed that amoxicillin release at pH = 7.4 was higher than at pH = 1.1. The analysis of the drug release showed that amoxicillin was released from these hydrogels through a non-Fickian diffusion mechanism. (c) 2007 Society of Chemical Industry.