In the present study we have developed a non-effervescent gastro retentive dosage form containing pantoprazole sodium by emulsion solvent diffusion method. A 23 full factorial design was used for the optimization process and the various responses obtained were evaluated by fitting in the binomial equations. Formulations ERS 1-8 were made utilizing three independent variables such as amount of crospovidone (%), Eudragit®E100 (mg) and Eudragit®RS100 (mg) which were varied at low and high levels and are evaluated for percentage buoyancy, entrapment efficiency and cumulative drug release after 5 h in buffer pH 2.2. The experimental values of the optimized formulation ERS-O coincides well with the predicted values obtained from optimization technique. Design expert 9.0.3 predicts responses as % buoyancy of 75.04±0.05, % entrapment efficiency of 87.57±0.21 and cumulative drug release after 5 h of 97.93±0.15 which were close to the actual values validates the design. The optimized formulation were in size range 20-120 µm with spherical shape, internal hollow cavity and porous boundary wall, moreover only physical cross-linking occurred with zero order release pattern and the in vivo analysis through ethanol induced ulceration method gave better ulcer healing orally than the intravenous route.