Preparation and Evaluation of Novel pH-Sensitive Poly(butyl acrylate-co-itaconic acid) Hydrogel Microspheres for Controlled Drug Delivery RABIA RAZZAQ, NAZAR MOHAMMAD RANJHA, ZERMINA RASHID, AND BUSHRA NASIR Faculty of Pharmacy, Bahauddin Zakarayia University, Multan, Pakistan Correspondence to: Rabia Razzaq; e-mail: rrcapricon@yahoo.com. Received: September 10, 2015 Accepted: December 20, 2015 ABSTRACT: In this study, a series of novel pH-sensitive copolymeric butyl acrylate-co-itaconic acid (p(BA-co-IA)) hydrogel microspheres were prepared by modified suspension polymerization of butyl acrylate and itaconic acid with the addition of 5% ethylene glycol dimethacrylate as a cross-linker and 1% benzoyl peroxide as an initiator. Nifedipine, an antihypertensive drug, was successfully encapsulated into these hydrogel microspheres by the equilibrium swelling method. Prepared hydrogel micropsheres were evaluated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffractometry (XRD), thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC). The chemical stability of the nifedipine after being encapsulated into prepared hydrogel microspheres was confirmed by FTIR, DSC, and XRD analysis. TGA indicates that prepared samples showed much better thermal stability than pure drug nifedipine. SEM images showed that prepared p(BA-co-IA) hydrogel microspheres are spherical in shape. The size distribution of prepared samples was found between 4.145 to 10 μm using a Malvern nanosize ZS instrument. The maximum percentage entrapment efficiency of nifedipine was found 67%, and % yield was about 72%. The maximum in vitro release studies of drug-loaded microspheres, which is 94.4% for the pH 7.4 buffer solution, demonstrated the pH sensitivity of prepared hydrogel microspheres. The cumulative drug release data were analyzed by using the Korsmeyer–Peppas equation to calculate a value of diffusion exponent (n), which follows non-Fickian diffusion. C  2016 Wiley Periodicals, Inc. Adv Polym Technol 2016, 00, 21663; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.21663 KEY WORDS: Copolymer (butyl acrylate-co-itaconic acid), crosslinking, FT-IR, Hydrogel Microspheres, Swelling Introduction P harmaceutical technology has developed controlled re- lease (CR) formulations of certain drugs for their effective targeting to the site of action. The polymeric systems are used to develop CR formulations to achieve the maximum concentration of drug to the target site minimizing side the effects. 1 These hydrogel microspheres are composed of three- dimensional polymer chain networks that are cross-linked either by covalent or physical bonds. Amphiphilic hydrogel micro- spheres are designed by incorporating a hydrophobic moiety to the hydrophilic monomer will serve as an efficient system, with better loading of drugs and high mechanical stability. 2 These pH-sensitive carriers are suitable for oral drug delivery systems due to their small size and efficient carrier capacity. These gels are in intact form in the stomach, and the drug encapsulated into these gels remain intact whereas in neutral and basic medium of intestine gels are swollen and drug is released. 3 Contract grant sponsor: Faculty of Pharmacy, Bahauddin Zakarayia University, Multan, Pakistan. Itaconic acid (IA) has two carboxylic acid groups with dif- ferent pKa (pKa 1 = 3.85 and pKa 2 = 5.45, respectively) values. 4 It is highly hydrophilic due to two carboxylic groups, easily copolymerizes with hydrophobic monomer butyl acrylate (BA) to make stable hydrogel microspheres at higher pH values 5 . The double ionization of IA at different pH values provides the stepwise release of entrapped drug by controlling pH of the medium. 6 Nifedipine, an antihypertensive drug which is poorly water soluble and has a plasma half-life of 2 h, is used as a model drug for encapsulation into p(BA-co-IA) hydrogel. 7 The objective of the current study is to formulate, characterize, and evaluate the novel copolymeric pH-sensitive p(BA-co-IA) hydrogel microspheres. These hydrogel microspheres were pre- pared by a modified suspension polymerization technique us- ing different monomeric compositions of BA and IA and loaded with nifedipine as a model drug. The prepared samples were characterized by using different techniques including Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimeteric analysis (TGA), and X- ray diffractometry (XRD). The size and morphology of these hy- drogel microspheres were determined using scanning electron microscopy (SEM) and zeta analysis. In vitro release studies of Advances in Polymer Technology, Vol. 00, No. 0, 2016, DOI 10.1002/adv.21663 C  2016 Wiley Periodicals, Inc. 21663 (1 of 9)