The aim of this study was to develop a chitosan-poly(acrylic) acid based controlled drug release system for gastric antibiotic delivery. Different mixtures of amoxicillin (A), chitosan (CS), and poly(acrylic) acid (PAA) were employed to obtain these polyionic complexes. A non-invasive method was employed for determining the gastric residence time of the formulations. It was studied the swelling behavior and drug release from these complexes. Gastric emptying rate study was performed by means of the [13C]octanoic acid breath test. The gastric emptying rates of two different formulations (conventional and gastric retentive system) were studied. Swelling studies indicated that the extent of swelling was greater in the polyionic complexes than in the single chitosan formulations. The amoxicillin diffusion from the hydrogels was controlled by the polymer/drug interaction. The property of these complexes to control the solute diffusion depends on the network mesh size, which is a significant factor in the overall behavior of the hydrogels. The gastric half-emptying time of the polyionic complex was significantly delayed compared to the reference formulation, showing mean values of 164.32+/-26.72 and 65.06+/-11.50min, respectively (P<0.01). The results of this study suggest that, these polyionic complexes are good systems for specific gastric drug delivery.