International Journal of Biological Macromolecules 55 (2013) 6–14 Contents lists available at SciVerse ScienceDirect International Journal of Biological Macromolecules jo u rn al hom epa ge: www.elsevier.com/locate/ijbiomac Development of modified release gliclazide biological macromolecules using natural biodegradable polymers Vipulkumar D. Prajapati ∗ , Krupa H. Mashru, Himanshu K. Solanki, Girish K. Jani Department of Pharmaceutics, S.S.R. College of Pharmacy, Saily-Silvassa Road, Saily, Silvassa, U.T. of D.N.H. 396230, India a r t i c l e i n f o Article history: Received 11 November 2012 Accepted 3 December 2012 Available online 7 January 2013 Keywords: Gliclazide Natural biodegradable polymers Modified Release a b s t r a c t Modified release biological macromolecules (beads) of gliclazide using sodium alginate combined with either gellan gum or pectin in different ratios were prepared by Ionotropic gelation method. Biolog- ical macromolecules were evaluated for different physico-chemical parameters. Increase in polymers proportion showed difficulty in production of biological macromolecules due to high viscosity of disper- sion. As the polymer concentration increases, the swelling and entrapment efficiency of drug increased. Compared to all other batches and commercial modified release gliclazide tablet, formulated biological macromolecules of sodium alginate with pectin (2:1 ratio) and with gellan gum (6:0.75 ratio) exhibited spherical shape, biphasic in vitro release profile and initial high drug release followed by moderate release up to 12 h as matrix diffusion kinetics and Higuchi model as well as Korsmeyer model. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Gliclazide (GLZ) is a second generation of hypoglycemic sul- fonylurea and acts on pancreatic cell to control type II diabetes mellitus. Sulfonylureas have been used successfully for the treat- ment of type II diabetes and useful for islet cells function in those patients whose dietary and lifestyle modifications have proven to be insufficient [1,2]. Currently, patients have to rely on one or more doses of conventional or modified release (MR) GLZ oral tablets to maintain normal plasma glucose levels in the treatment of type II diabetes mellitus [3,4]. Currently, the GLZ tablets available in the market have not yet attained the physiological goal of providing constant plasma glu- cose levels over an extended period of time to meet the basic dietary needs between meals and dinner. Its plasma half life is 6–14 h. The bioavailability of GLZ MR tablets after administration of single oral dose of 30 mg is almost completed (97%) [5]. The release of GLZ over a 24 h period has been shown to parallel the circadian glycemic pro- file of type II diabetes [6]. In spite of the good clinical results of this MR tablet formulation, the binding of GLZ to sulfonylurea receptors on pancreatic cells is rapidly gets reversed, which indicates low rate ∗ Corresponding author at: Department of Pharmaceutics and Pharmaceutical Technology, SSR College of Pharmacy, Saily-Silvassa Road, Saily, Silvassa, U.T. of Dadra and Nagar Haveli 396 230, India. Tel.: +91 09824284159; fax: +91 0260 2681104. E-mail address: vippra2000@yahoo.com (V.D. Prajapati). of hypoglycemia and pancreatic exhaustion resulting in failure of MR GLZ tablet formulation. Compared to non-disintegrating type oral single-unit dosage forms, microspheres and biological macromolecules (beads) type oral multiple-unit solid dosage forms are under limelight for sev- eral years due to numerous reasons such as they provide more uniform distribution and absorption of the drug in the gastrointesti- nal tract, reduction in local irritation, and elimination of unwanted intestinal retention of polymeric material [7]. Over the past two decades hydrogel biodegradable polymers is preferred for use as potential carriers in modifying release of drugs as well as site- specific delivery of drugs. There has been growing interest in use of natural biodegradable polymers as drug carriers, due to their bio- compatibility and biodegradability. Various natural biodegradable polymers like alginates or sodium alginate (SA), pectin, gellan gum, chitosan, guar gum, agar, carrageenan have been used in MR drug delivery development. These biodegradable polymers have been utilized either alone or in combination to make an interpenetrating polymeric network (IPN) between their chains to develop desired modified release dosage form of drugs using suitable cross-linker like calcium chloride (CaCl 2 ). Alginate is naturally occurring polysaccharide obtained from marine brown algae (seaweeds) consisting of two monomeric units, -d-mannuronic acid (M) and -l-guluronic acid (G). These residues are arranged in homopolymeric blocks (MG). Alginates show gelling properties in the presence of divalent cations like Ca ++ , Sr ++ or Ba ++ . It was reported that alginate is nontoxic and biodegrad- able when administered orally. Alginate has been used in food additives as stabilizer and gelling agent, and also in pharmaceutical 0141-8130/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijbiomac.2012.12.033