Research in Pharmaceutical Sciences, October 2008; 3(2): 1-8 School of Pharmacy & Pharmaceutical Sciences Received: Apr 2008 Isfahan University of Medical Sciences Accepted: Aug 2008 Original Article *Corresponding author: Mrs. Vaishali T. Thakkar Tel. 0091 02692 250020 Email: vtthakkar@rediffmail.com Fabrication and evaluation of levofloxacin hemihydrate floating tablet V.T. Thakkar 1,* , P.A. Shah 1 , T.G. Soni 1 , M.Y. Parmar 1 , M.C. Gohel 2 and T.R. Gandhi 1 1 Department of Pharmaceutics, Anand Pharmacy College, Anand- 388001 Gujarat, India. 2 Department of Pharmaceutics, L. M. College of Pharmacy, Ahmedabad- 380009, Gujarat, India. Abstract The objective of this work was to develop and evaluate the levofloxacin hemihydrate floating formulations (F1-F9). Selection of optimized batch was done by model dependent approach and novel mathematical approach. F1-F9 batches were prepared by direct compression method using Gelucire 43/01 (hydrophobic) and hydroxypropylmethylcellulose (hydrophilic) polymer in different ratios. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, in vitro buoyancy and in vitro release studies. Various models were used to estimate kinetics of drug release. The criteria for selecting the most appropriate model were based on the goodness-of-fit test and lowest sum of square residual and Fischer’s ratio. In vitro release study reveals that the release rate of drug was decreased by increasing the proportion of Gelucire 43/01, 5 to 40%. The release rate of levofloxacin hemihydrates from matrices was mainly controlled by the hydrophilic and hydrophobic polymer ratio. Matrix tablet containing 25% HPMC K4M and 15% Gelucire 43/01 (F4 batch) showed a release as target profile. Optimal batch (F4) was selected by regression analysis which followed Higuchi kinetic. Novel mathematical approach was applied to determine the deviation in area under the curve (AUC) between predicated and observed dissolution data which found to be lowest in optimal batch. The drug release was found to be function of ratio of hydrophobic to hydrophilic matrixing agents. Keywords: Levofloxacin hemihydrate; Floating tablet; Hydroxypropylmethyl cellulose; Gelucire INTRODUCTION In a relatively short time span, Helicobacter pylorus (H. pylori) has been recognized as a major gastric pathogen with worldwide distribution (1). H. pylori, human-specific pathogen, is a causative organism in chronic active gastritis, duodenal ulcers and gastric adenocarcinoma (2,3). The pathogen is susceptible to many antibiotics in vitro but it is difficult to eradicate it in vivo (4). Extended resident time of the antimicrobial agents is desirable for effective eradication of H. pylori (1,5). In order to extend the gastric residence period, a number of approaches have been developed such as floating drug delivery systems, swelling and expanding systems, polymeric bioadhesive systems, modified- shape systems, high-density systems and other delayed gastric emptying devices (6-8). Levofloxacin hemihydrate, a synthetic fluorinated quinolone derivative, is effective for the treatment of H. pylori (9-12). The failure of the antibiotic therapy can be avoided by providing the effective concentration of drug at the site of action (13). In the present study, an attempt has been made to formulate levofloxacin floating tablets with the use of hydroxypropyl methyl cellulose (HPMC K4M) and release-retarding hydrophobic polymer Gelucire 43/01. Gelucire, chemically the mixtures of mono-, di- and tri-glycerides with polyethylene glycol (PEG) esters of fatty acids, was used in the combination with hydrophilic polymer, HPMC K4M, to control the release of highly water soluble levofloxacin hemihydrates. The change in composition of matrixing agents may influence the change in mechanism of drug release. It is therefore, very essential that the formulated products release the drug by the same mechanism for drawing meaningful conclusion in research. If the kinetics of drug release is known, it can also be advanced for the