613 Development and characterization of pH-sensitive locust bean gum-alginate microspheres for controlled release of ibuprofen E. Bulut 1 *, M. Dilek 2 1 Department of Chemistry, Science & Arts Faculty, 2 Chemical Engineering Department, Faculty of Engineering, Afyon Kocatepe University, 03200, Afyonkarahisar, Turkey *Correspondence: ebulut@aku.edu.tr In this study, interpenetrating polymer network (IPN) microspheres, consisting of locust bean gum (LBG) and sodium alginate (NaAlg), were prepared by a water-in-oil (w/o) emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker. These microspheres were loaded with ibuprofen (IBU), a nonsteroidal anti-inflammatory drug. The influence of formulation factors such as the LBG/NaAlg (w/w) ratio, the IBU loading percentage (w/w), the amount of cross-linker and cross-linking time on the particle size, the entrapment efficiency, and the release of IBU from the microspheres, were evaluated. The IPN microspheres were characterized using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Images of selected microspheres were determined using an optic microscope. The in vitro release of IBU from IPN microspheres was investigated at three pH values (1.2, 6.8 and 7.4) for 2 h, respectively. The release of IBU increased with the increase of the drug loading percentage (w/w), while it decreased with the increasing extent of cross-linking and with the increase in blend ratio (LBG/ NaAlg). The release results indicated that IPN microspheres of LBG and NaAlg exhibited a more controlled release property than plain NaAlg microspheres. IBU release from the microspheres followed either Fickian transport or anomalous transport. Key words: Locust bean gum – Sodium alginate – Ibuprofen – Drug delivery systems. J. DRUG DEL. SCI. TECH., 24 (6) 613-619 2014 In recent decades, biopolymers, especially polysaccharides, have been widely used in useful applications in the biomedical and, specifically, in the biopharmaceutical fields [1], because the natural polysaccharides originating from renewable resources are abundant, comparatively cheap, nontoxic, and biodegradable [2]. Thus, much research has focused on the use of polysaccharides for the development of drug delivery systems [3]. Among various natural polysaccharides which have been employed, chitosan [4, 5], alginate [6, 7], dextran [8], xanthan gum [3], and locust bean gum [9] have been extensively studied for the production of drug delivery systems. Polymeric-controlled drug delivery systems being one of the most rapidly advancing areas of science, offer numerous advantages compared to conventional dosage forms, such as reduced toxicity, improved efficacy, and improved patient compliance and convenience [10]. Such formulations have the ability to incorporate drugs without altering their integrity and maintain excellent in vivo compatibility. Among these structures, polymeric hydrogels are potential candidates in drug delivery research, because their porous structure allows for the easy transport of the incorporated drug in a controlled manner [11, 12]. However, the major disadvantage of hydrogels is their poor mechanical properties as a result of extensive swelling [13]. Therefore, a visible interest has been dedicated to the improvement of interpenetrating polymer network (IPN) systems as a rapidly developing branch of polymer technology [12]. An IPN consists of two or more polymers, where one of the networks is cross-linked in the presence of the other [14], and materials formed from IPN share the properties of each network. Thus, IPN structures of two or three different polymers are better choices [12]. These IPN systems are preferred in a number of biomedical and biotechnological applications due to their certain unique biophysical properties such as ease of fabrication to various geometrical forms, a soft and rubbery texture, minimum mechanical irritation to surrounding tissues, and unusual stability to biofluids [15]. Sodium alginate is a biopolymer obtained from marine brown algea and consists of β-D-mannuronic acid and α-L-guluronic acids [3]. It is used as the most common encapsulation material due to its simplicity, non-toxicity, biocompatibility, and low cost [16, 17]. Al- ginate is pH sensitive and stable in the acidic pH environment of the stomach, but it swells and starts dissolving in the intestinal alkaline pH environment [18]. Besides, alginate microspheres with a porous structure allow the diffusion of acid in and out of microspheres easily [17]. These disadvantages can be overcome by blending alginate with other polymers or coating one polymer layer on alginate microspheres [19, 20]. For this reason, in the study, LBG/NaAlg IPN microspheres were prepared to provide more controlled release conditions and to increase the strength of the alginate microspheres. Locust bean gum (LBG), a non-ionic natural polysaccharide, is a high molecular weight branch polysaccharide, which consists of a linear chain of β-D mannopranosil units linked to 1,4 single, α-D galactopranosil units linked to 1,6 of the main chain at side branches [21, 22]. It is also known as carob bean gum and is extracted from the seeds of the carob tree. It is a neutral polymer and its solubility and viscosity are little affected by pH changes within the range of 3-11 [1, 22]. Blends of LBG with other polymers have been reported in the literature [9, 22-24]. Dey et al. [9] studied the gastrointestinal delivery of glipizide from carboxymethyl locust bean gum-Al 3+ -alginate hydrogel network and its performance was evaluated both in vitro and in vivo. They found that an increase in the degree of cross-linking and in the carboxymethyl locust bean gum weight ratio in the interpenetrating polymer network (IPN) was found to increase the mean dissolution time of the encapsulated drug and the IPN showed significant hypo- glycemic activity on male wistar rats for up to 10 h. Kaity et al. [22] developed IPN microspheres of LBG and poly(vinyl alcohol) (PVA) for oral controlled release of buflomedil hydrochloride (BH) and reported that the IPN of LBG and PVA microspheres can be used as a potential carrier for controlled oral delivery of highly water soluble drugs like BH. Watanabe et al. [23] investigated the release behavior of prednisolone from hydrogels prepared with xanthan and locust bean gums. They reported that drug release could be controlled not only by the density of the network structure but also by the microscopic viscosity of the hydrogels. In this study, we have developed a natural, biodegradable inter- penetrating polymer network system containing ibuprofen (IBU) for