Chitosan is a natural polymer which has limited solubility. Chitosan gets solubilized at acidic pH but is insoluble at basic pH. In the present study, carboxymethyl chitosan (CMC) was prepared which shows high swelling in basic pH and thus can delay the drug release and can act as matrix for extended release formulation. CMC was characterized by FTIR and NMR. pH-sensitive hydrogels of theophylline were formulated using CMC and carbopol 934. Hydrogels were evaluated for swelling, drug content in vitro drug release studies, and in vivo studies on rabbit. The swelling studies have shown little swelling in acidic pH 432% at the end of two hours and 1631% in basic pH at the end of 12 hours. The release profile of the formulation I containing CMC and carbopol in 1？:？1 ratio showed sustained release. In vivo studies showed that the release of theophylline from the prepared hydrogel formulation (Test) exhibit better prolonged action when compared to (standard) marketed sustained release formulation. The studies showed that the pH-sensitive hydrogel of CMC can be used for extended release of theophylline in intestine and can be highly useful in treating symptoms of nocturnal asthma. 1. Introduction Chitosan is biodegradable and biocompatible polymer. Since chitosan is insoluble in water, the use of chitosan in basic environment is limited and hence delivery of drugs to the intestine is not possible. A derivative of chitosan, that is CMC, is soluble in water [1, 2]. Amphoteric polyelectrolyte hydrogels possessing both positive and negative charges, and many researchers are using amphoteric polyelectrolyte hydrogels to develop controlled delivery systems such as an insulin pump for diabetics, matrices for molecular recognition or separation, and so forth. A lot of research is going on the stimuli-sensitive polymer hydrogels. Among stimuli-sensitive systems, pH or temperature-responsive hydrogels have been extensively studied in the biomedical field, because these two factors can be easily controlled and are applicable both in vitro and in vivo conditions [3, 4]. CMC is amphoteric polyelectrolyte and has various applications due to its unique chemical, physical, and biological properties, especially its excellent biocompatibility. It is used to prepare wound dressings, artificial bone, and skin, is used as a bacteriostatic agent and blood anticoagulant also. It has also demonstrated good pH and ion sensitivity in aqueous solutions due to abundant –COOH and –NH2 groups [5]. Recent studies have shown that CMC has been used in preparation of nanoparticles for
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