EXPERIMENTAL DESIGN APPROACH TO FABRICATE AND OPTIMIZE FLOATING TABLETS OF LEVOFLOXACIN FOR HELICOBACTER PYLORI INFECTION Original Article JAGANATHAN K. 1,2 , VENKATESWARAMURTHY N. 2 , NEELAMEGARAJAN R. 2 , KANNAN C. 2 , SAMBATHKUMAR R. 2* 1 The Tamilnadu Dr MGR Medical University, Chennai, Tamilnadu, India 600032, 2 Department of Pharmaceutics, J. K. K. Nattraja College of Pharmacy, Kumarapalayam, Tamilnadu, India 638183 Email: sambathju2002@yahoo.co.in Received: 28 Jul 2022, Revised and Accepted: 22 Sep 2022 ABSTRACT Objective: To improve the treatment of H. pylori infection, by achieving the required bactericidal concentrations of antibiotics in the stomach, by delivering the antibiotics to the mucus layer and release the drug at the site of infection for a prolonged period would be significantly more effective than conventional dosage forms. Methods: The experimental method of the research was designed to prepare Levofloxacin floating by using Hydroxypropyl Methylcellulose (HPMC K4M), Hydroxypropyl Methylcellulose (HPMC K100M) and Xanthan gum by Three-level Box–Behnken design optimization method. The prepared tablets were evaluated for Thickness, Hardness, Friability, Weight variation, Swelling index (SI), Floating lag time (FLT) and Time required to release 90% of the drug from the tablet (T90%). Results: It was found that the Thickness-3.12±0.11 mm to 3.28±0.10 mm, Hardness-4.52±0.36 kg/cm 2 to 4.81±0.24 kg/cm 2 , Friability-0.81±0.02g to 0.86±0.12g, Weight variation-480±1.90 mg to 523±0.89 mg, Swelling index (SI)-61.9±0.624% to 99.95±0.226%, Floating lag time (FLT)-81.12±0.63 s to 119.7±0.567 s and Time required to release 90% of the drug from the tablet (T90%)-7.0±0.55 h to 10.33±0.289 h. HPMC K100M and Xanthan gum showed good swelling as compared to HPMC K4M. The study revealed that HPMC K100M grade had a significant effect on drug release. Conclusion: The developed gastro-floating tablets can extend levofloxacin duration in the stomach and produce a prolonged release effect. The prepared levofloxacin floating tablet oral drug delivery system appears to be a promising choice for the efficient eradication of H. pylori Keywords: Levofloxacin, Floating tablet, Helicobacter pylori, Box–Behnken design, HPMC K4M, HPMC K100M, Xanthan gum © 2022 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/) DOI: https://dx.doi.org/10.22159/ijap.2022v14i6.45809. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Helicobacter pylori (H. pylori) is a gram-negative bacterium found in the stomach of about half of the world's population [1]. H. pylori infection is a strong risk factor for gastroduodenal ulcer disease, gastric cancer, and other types of gastric and extra gastric disease. This infection is linked up to 85% of gastric ulcers and 95% of duodenal ulcers, and eliminating the organism reduces the risk of ulcer recurrence dramatically [2]. The World Health Organization's (WHO) International Agency for Research on Cancer (IARC) classified H. pylori as a "category 1" pathogen (definite carcinogen) and suggested that H. pylori eradication is considered to lower the risk of stomach cancer, which kills 738,000 people worldwide each year. According to reports, eradicating H. pylori lowers the risk of stomach cancer [3, 4]. The Maastricht V Consensus Report and the guidelines established by the American College of Gastroenterology both suggested using levofloxacin-based triple therapy as a second- line treatment option [5, 6]. However, eradicating H. pylori successfully and completely has become a challenge in recent years. Recent biopsy studies [7, 8] and cell culture infection models have indicated that H. pylori penetrate the gastric mucus layer and attach to various phospholipids and glycolipids in the mucus gel. As a result, both the lumen of the stomach and the gastric blood supply limit antibiotic availability in the mucus layer for a prolonged period. Also, the traditional drug delivery systems do not stay in the stomach for extended periods, and they are unable to deliver adequate concentrations and fully active antibiotics to the infection site. There is a need for new drug delivery systems to address the inadequacies of conventional delivery systems. Floating drug delivery systems have a bulk density lower than that of gastric fluids, allowing them to stay buoyant and deliver the drug for a longer period of time in the stomach without being impacted by the gastric emptying rate. Hence, in the present study, gastro retentive floating Levofloxacin tablets for the eradication of H. pylori, were prepared using Xanthan gum, HPMC K100M and HPMC K4M and evaluated to overcome the shortcomings of conventional delivery of levofloxacin. MATERIALS AND METHODS Materials Xanthan gum was purchased from SD Fine Chem Limited, Mumbai. HPMC K100M and HPMC K4M and Levofloxacin hemihydrate were gifted by MICRO LABS LIMITED, Bengaluru. All other used solvents were HPLC grade. Experimental design A three-factor, Three-level Box–Behnken design was used for the optimization procedure using Design-Expert® 13 software (Stat-Ease, Inc., USA). The investigated factors (independent variables) were HPMC K4M (A1) content HPMC K100M (B2) and Xanthan gum content (C3). The levels for these three factors were determined from sufficient preliminary trials. The Swelling index (SI), Floating lag time (FLT) and Time required to release 90% of the drug from the tablet (T90%) were selected as dependent variables as shown in table 1. The experimental design with the corresponding formulations is outlined in table 2. The statistical model: Y = b 0 + b 1 A + b 2 B + b 3 C + b 11 AA + b 22 BB + b 12 AB + b 23 BC + b 13 AC + E Compatibility studies Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) was used to study the compatibility of Levofloxacin with excipients. Fourier transform infrared (FTIR) spectroscopy FTIR spectra of Levofloxacin, excipients and physical mixtures (drug: excipient ratio of 1:1) were recorded in the wavelength region 500-4,000 cm -1 using FTIR 8400S (Shimadzu, Japan). International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 14, Issue 6, 2022