Full Proceeding Paper FORMULATION AND EVALUATION OF BUOYANT TABLETS OF KETOCONAZOLE GHOSH T. * , S. BHARATH, NAIK R., B. V. BASAVARAJ, R. DEVESWARAN Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, MSR Nagar, Bangalore, Karnataka Email: tanmoy.ps.ph@msruas.ac.in Received: 13 Dec 2018, Revised and Accepted: 18 Mar 2019 ABSTRACT Objective: The primary objective of the present work was to formulate the gastro-retentive delivery system of ketoconazole (ktz) for its extensive absorption in the stomach. Methods: The solubility and dissolution of antifungal ktz were reported to be higher in the stomach than in the intestinal pH conditions because of its dibasic pKa values 6.51 and 2.94. Thus the development of target buoyant tablets using Hydroxy Propyl Cellulose (HPC) and Xanthan gum (Xg) as polymers along with the effect of citric acid and sodium bicarbonate as an effervescent causing agent of floatation properties and drug release profile was investigated. The formulation optimization was carried out by using a central composite design using Design Expert software by taking HPC, Xanthan gum and sodium bicarbonate as independent variables and floating lag time, in vitro drug release profile as dependent variables respectively. Results: The optimized formulation of ktz buoyant tablets could be developed. The amount of HPC and Xg was found to significantly influence all in vitro response parameters. The results of pre-compression and post-compression parameters of all the formulations were found to be within the standard limits. The optimized formulation exhibited floating lag time of 160 secs with sustained drug release over a period of 12 h in simulated stomach pH condition. Conclusion: Buoyant tablets of ktz with sustained drug release over a period of 12 h in simulated stomach conditions for enhanced drug absorption could be successfully developed. Keywords: Buoyancy, Gastro-retentive drug delivery, Ketoconazole, Optimization design © 2019 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ijap.2019v11si2.31318 INTRODUCTION ktz is a broad-spectrum anti-mycotic drug having two pKa values(6.51 and 2.94) with poor water solubility and short elimination half-life of 2 h [1]. It is a drug of choice for treatment of candidiasis, oral thrush, candiduria and paracoccidioidomycosis. It has been reported that the solubility and dissolution of ktz have found to be increased in the stomach pH than in the intestinal pH conditions. Thus in the present study, an attempt has been made to formulate ketoconazole into a floating drug delivery system to prolong its gastric residence time with an increase in its dissolution and absorption. As for reliable retention behavior in the stomach, the design of dosage form, food effects and the complex motility of the stomach poses a major challenge to the formulator [2]. The controlled gastric retention of solid dosage forms may be achieved by the mechanisms of mucoadhesion [3, 4] flotation, sedimentation [5, 6] expansion, modified shape systems [7, 8] or by the simultaneous administration of pharmacological agents [9, 10] that delay gastric emptying. The floating drug delivery system (FDDS) have a bulk density lower than gastric fluid and thus remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. Based on the mechanism of buoyancy, two distinctly different technologies, i.e. with effervescent and without effervescent systems have been used in the development of FDDS. The effervescent system uses matrices prepared with swellable polymers and effervescent components e. g. sodium bicarbonate and citric acid or tartaric acid. In non-effervescent FDDS, the drug mixes with a gel- forming hydrocolloid, which swells in contact with gastric fluid after oral administration to maintain a relatively stable shape and a bulk density of less than unity within the outer gelatinous barrier. The air trapped by the swollen polymer confers buoyancy to these dosage forms [11]. In the present investigation, an attempt to increase the dissolution was made by developing gastro-retentive floating tablets of ktz using HPC, Xg as a gel-forming agent and also release retardant agent with citric acid-sodium bicarbonate as effervescent components. MATERIALS AND METHODS ktz and Xg were purchased from Yarrow chem. Product, Mumbai. HPC was purchased from Himedia Laboratories Pvt. Ltd, Mumbai. All other ingredients, reagents and solvents were of analytical/ laboratory grade. Design of formulations Formulations were developed using a central composite design after results obtained through conducted pre-formulation trials. The Design-Expert Software (version 8.0.1, Stat-Ease Inc., Minneapolis, USA) suggested eight model formulations as shown in table 1 considering the concentration of HPC, Xanthan gum and sodium bicarbonate as independent variables with the percentage drug release, floating lag time as dependent variables. Table 1: Central composite design response for three factors Run Formulation code Type Factor 1: A HPC Factor 2: B xanthan gum Factor 2: B sodium bicarbonate 1 OFT-1 Factorial 50 50 50 2 OFT-2 Factorial 50 150 50 3 OFT-3 Factorial 150 150 100 4 OFT-4 Factorial 150 150 50 5 OFT-5 Factorial 150 50 100 6 OFT-6 Factorial 150 50 50 7 OFT-7 Factorial 50 150 100 8 OFT-8 Factorial 50 50 100 International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 11, Special Issue 2, 2019