Preparation, in vitro and in vivo evaluation of stomach-specific metronidazole-loaded alginate beads as local anti-Helicobacter pylori therapy Rania A.H. Ishak a, ⁎ , Gehanne A.S. Awad a , Nahed D. Mortada a , Samia A.K. Nour b a Department of Pharmaceutics, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt b Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Cairo, Egypt Received 10 May 2006; accepted 16 February 2007 Available online 1 March 2007 Abstract Metronidazole (MZ), a common antibacterial drug used in treatment of H. pylori, was prepared in chitosan-treated alginate beads by the ionotropic gelation method. A (3 × 2 × 2) factorially designed experiment was used in which 3 viscosity-imparting polymers namely, methyl cellulose, carbopol 934P and κ-carrageenan, 2 concentrations (0.2 and 0.4% w/v) of chitosan as encapsulating polymer and 2 concentrations (2.5 and 5% w/w) of the low density magnesium stearate as a floating aid were tested. The drug entrapment efficiency (%), the percent of floating beads and the time for 80% of the drug to be released (T 80% ) were the responses evaluated. The bead formula containing 0.5% κ-carrageenan, 0.4% chitosan and 5% magnesium stearate showed immediate buoyancy, optimum drug entrapment efficiency and extended drug release. The histopathological examination of mice stomachs and in vivo H. pylori clearance tests were carried out by orally administering MZ floating alginate beads or MZ suspension, to H. pylori infected mice under fed conditions as a single daily dose for 3 successive days in different doses 5, 10, 15 and 20 mg/kg. The histopathological examination showed that groups receiving MZ in the form of floating alginate beads at doses 10, 15 and 20 mg/kg were better than the corresponding suspension form, regarding eradication of H. pylori infection. The in vivo H. pylori clearance tests showed that MZ floating beads with a dose of 15 mg/kg provided 100% clearance rate whereas the MZ suspension with a dose of 20 mg/kg gave only 33.33%. © 2007 Elsevier B.V. All rights reserved. Keywords: Alginate beads; Floating drug delivery systems (FDDS); Metronidazole; Sustained release; H. pylori clearance; Local delivery 1. Introduction The local treatment of H. pylori with conventional tablets or capsules may fail, since these may fall to the base of the stomach from where they are readily emptied [1]. Little, if any, drug is delivered to the body or fundus of the stomach and the main drug action is through systemic effect. Various approaches have been pursued to increase the retention of an oral dosage form in the stomach, including swelling and expanding systems [2,3], bioadhesive systems [4,5], modified- shape systems [6,7], high-density systems [8] and floating systems [9]. Floating drug delivery systems (FDDS) with low bulk density will remain buoyant in the stomach without being affected by the gastric emptying rate for a prolonged period of time. While the system is floating on the gastric contents, the drug is slowly released at a desired rate [10]. Multiple-unit FDDS show several advantages over monolithic ones, among which: avoiding all-or-nothing emptying, absence or impairing of performance due to failure of a few units, more predictable drug release kinetics, less chance of localized mucosal damage and administration of units with different release profiles or those containing incompatible substances [11]. However various floating alginate beads suffered from rapid drug release for drugs [12,13], a problem which was overcome by addition of further additive [14]. Recently, gastroretentive systems for treating H. pylori have shown special interest. The prolongation of the local availability of the antibacterial agents has been reported to be an important factor to increase the effectiveness of H. pylori treatment [15]. This will ensure a high drug concentration in the gastric mucosa Journal of Controlled Release 119 (2007) 207 – 214 www.elsevier.com/locate/jconrel ⁎ Corresponding author. E-mail address: raniaaziz77@yahoo.com (R.A.H. Ishak). 0168-3659/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.jconrel.2007.02.012