pH – responsive biodegradable semi- interpenetrating polymeric network (semi- IPN) hydrogels microspheres based on Chitosan and PVA were prepared and Characterized for the controlled drug release investigations. Glutraldehyde was used as a crosslinking agent. The equilibrium swelling Characteristics were investigated for the hydrogel microspheres at 370C in buffer solution at pH 2.1 (simulated gastric fluid, SGF) and pH 7.4 simulated intestinal fluid, SIF). Clarithromycin was entrapped in the hydrogels for stomach-specific drug delivery system for controlled release of drug for eradication of Helicobacter pylori (H. pylori); in vitro release profiles of the drug were established at 370 C at pH 2.1 and pH 7.4. FTIR, SEM was used to characterize hydrogels.