The present work reported the synthesis of pH-responsive hybrid polymer network (HPN) of chitosan and gelatine by using glutaraldehyde as a cross-linker. Different reaction parameters like backbone ratio, amount of solvent, pH, the time, the temperature of reaction mixture and concentration of cross-linker were optimized with response surface methodology in order to maximize the percentage swelling. The maximum percentage swelling was obtained 530.48% under most optimized conditions of the ratio (1:1), pH (7) and cross-linker (0.241mol/l). Poor loading of drug in traditional drug delivery is improved by incorporating preformed inclusion complex of chlorphenamine maleate (CPM) with -cyclodextrin (1:1) under microwave conditions directly into the HPN matrix. Further, HPN matrix was used to investigate the in situ controlled release of CPM under different pH conditions at 37 degrees C. CPM release showed the best fit to the Peppas-Sahlin equation under all pH conditions at 37 degrees C. Thus, HPN prepared by using RSM design is a good device to deliver the CPM in a controlled manner. [GRAPHICS] .