Hydrogels with tunable properties are of great interest for the development of advanced drug delivery systems. In this study, novel hydrogels with an interpenetrating polymer network (IPN) structure were obtained from the pH-responsive poly(methacrylic acid) (PMAA) and the neutral poly(N,N-dimethylacrylamide) (PDMAM). The newly synthesized IPN hydrogels were shown to be pH responsive with a 1.5 to 2.5 fold increase in their equilibrium swelling ratio at a pH above 5 which makes them appropriate for targeted intestine drug delivery. Moreover, their pH responsiveness was found to be strongly influenced by the IPN’s composition. The IPN hydrogels were loaded with PMH via swelling and the drug entrapment efficiency was found to depend on their swelling characteristic varying with the IPN’s composition from 20% to 60%. The drug release profiles were investigated under conditions resembling the oral route of drug application. The PMH release profiles appeared to follow Fickian diffusion at a stomach-like pH = 1.2 and sub-diffusion mechanism at an intestine-like pH = 6.8. The results from this study reveal that IPN hydrogels of PMAA and PDMAM are promising candidates for oral delivery of promethazine hydrochloridee demonstrating pH responsiveness and controllable swelling dependent on their composition. Further investigations are planned to fully reveal their potential as smart drug delivery systems.