Abstract: Ranitidine hydrochloride has a short biological half-life (2.1±0.2 h) and 50% absolute bioavailability. Development of sustained release formulation of ranitidine hydrochloride can be advantageous, that can provide prolong gastric retention and increase efficacy of the dosage form. Calculate theoretical release profile from floating matrix tablets of ranitidine and perform the drug excipient interaction study. In vitro dissolution studies, dissolution profiles, drug: polymer ratio, effect of low density copolymer PSDVB on the release profile of chitosan-carbopol 940 floating matrix tablets, geometry on release, effect of diluents were performed. Select the best batch and swelling index, kinetic modeling of drug release, accelerated stability and in vivo study were carried out. No chemical interaction between ranitidine hydrochloride and the polymers used. Result shows loss of integrity with the increase in concentration of carbopol 940. Significant changes in the floating lag time of the formulation with increased amount of co-polymer. With increasing initial tablet radius, the volume of the system and, thus, the amount of drug available for diffusion increases, resulting in increased absolute amounts of drug released. In contrast, the relative surface area of the device decreases and the amount of drug released in%/ time unit decreased. The x-ray and swelling index shows significant result in batch A12. The present investigation shows that the chitosan-carbopol 940 mixed matrices can be used to modify release rates in hydrophilic matrix tablets prepared by direct compression.