Poly(N-isopropylacrylamide) Hydrogel: Effect of Hydrophilicity on Controlled Release of Ibuprofen at Different pH Raju Francis, 1 * Deepa K. Baby, 1 D. Sakthi Kumar 2 1 Post Graduate and Research Department of Chemistry, St. Joseph’s College Devagiri (NAAC ‘A’ and College with Potential for Excellence, UGC), Calicut-673008, Kerala, India 2 Bio Nano Electronics Research Center, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Saitama, 350-8585, Japan Received 13 July 2010; accepted 7 September 2011 DOI 10.1002/app.35644 Published online 12 December 2011 in Wiley Online Library (wileyonlinelibrary.com). ABSTRACT: Stimuli-sensitive drug delivery systems (DDSs) have attracted considerable attention in medical and pharmaceutical fields; thermo-sensitive DDS dealing with poly(N-isopropylacrylamide) (PNIPAM) have been widely studied. Hydrogels composed of temperature-sen- sitive NIPAM and biocompatible and pH-sensitive maleic acid (MAc) were synthesized by sedimentation polymer- ization. Experiments on drug release from the crosslinked NIPAM-co-MAc hydrogel loaded with ibuprofen into dif- ferent pH buffer solutions were successfully carried out at temperature swing between 25 and 40  C. The in vitro release studies have showed that the release rate depended on acidity or basicity (polarity) of the medium and the gel and swelling ratio of the gel network as a function of the environmental pH and temperature. The SEM image of the dry bead gave more insight into the sur- face architecture and the thermal studies shine light on the decomposition pattern and glass transition temperature of the gel. The mechanism of the drug release was discussed in relation to the diffusion rate and the abrupt change in the pH of the medium. V C 2011 Wiley Periodicals, Inc. J Appl Polym Sci 124: 5079–5088, 2012 Key words: stimuli-sensitive polymers; drug delivery systems; hydrogels; biological applications of polymers; swelling INTRODUCTION The application of synthetic hydrogels started in the late 1950s’ when for the first time contact lenses were made. 1,2 Hydrogels are crosslinked polymeric ‘‘swell gels,’’ 3 they swell in aqueous solutions with- out dissolving in them. When a hydrogel is in a dry state, the density of polymer chains are high, allow- ing little room for molecular diffusion. As the hydro- gel swells and attains an equilibrium swelling value, the swelling pressure on the chains is counteracted by the force holding the chains together, namely, the force of crosslinking. At this equilibrium value, the molecular diffusion reaches its peak values. 4–15 Controlled release of drug molecules from hydro- gel is a technique well reported in the literature. 6–15 Temperature is a commonly used triggering signal for modulating drug release because of physiological relevance. 16–18 There are large numbers of polymeric materials investigated for this purpose. However, one polymer, poly(N-isopropylacrylamide) (PNI- PAM), stands out particularly due to its volume phase transition temperature (VPTT or LCST) near the body temperature. 19–22 In addition, the LCST of PNIPAM can be suitably tuned by incorporating hydrophilic/hydrophobic comonomers. 23–29 Polymers containing pendant carboxylic groups are typical acidic pH-responsive polymers. 30 Hydro- gels containing carboxylic groups exhibit pH-sensi- tive swelling-deswelling behaviors and are widely used in controlled drug delivery systems. 14,31–33 The combination of pH and temperature response is par- ticularly useful to optimize the control of drug release and a variety of hydrogels being sensitive to both pH and temperature have been synthesized. Most of these double-responsive hydrogels are IPN or semi-IPN being composed of pH-responsive part and temperature-responsive part. 34,35 Vasile et al. were able to demonstrate nonphase separable PNIPAM-graft-poly(MAc-alt-vinyl acetate) for thermothickening behavior in semi-dilute aque- ous solution. 36 Maleic acid (Mac)-based NIPAM *Present address: School of Chemical Sciences, Mahatma Gandhi University, Kottayam, Kerala-686560, India.. Correspondence to: R. Francis (rajufrancis@yahoo.com). Contract grant sponsor: DST-FT, SERC, Government of India; contract grant number: SR/FTP/CSA-17/2003. Contract grant sponsor: CSIR EMR Scheme, Government of India; contract grant number: 01(2201)/07/EMR-II. Journal of Applied Polymer Science, Vol. 124, 5079–5088 (2012) V C 2011 Wiley Periodicals, Inc.