Original Article OPTIMIZATION, DEVELOPMENT AND EVALUATION OF REPAGLINIDE CONTROLLED RELEASE GASTRO-RETENTIVE FLOATING TABLET USING CENTRAL COMPOSITE DESIGN MAHENDRA PATEL * , MASHEER AHMED KHAN School of Pharmacy, Devi Ahilya Vishwavidyalaya, Indore Email: mpatel533@gmail.com Received: 30 Sep 2022, Revised and Accepted: 08 Nov 2022 ABSTRACT Objective: The recent study's objective was to optimize and formulate a controlled-release gastro-retentive floating tablet of RG using a central composite design, which provides continuous release of Repaglinide for up to 24 h. Methods: Repaglinide gastro-retentive floating tablet (RG-GRF Tablet) was prepared by direct compression method. The optimization was carried out using a three-factor and three-level Central Composite design. The amount of Eudragit RSPO (A), HPMC K-100M (B) and Sodium bicarbonate (C) were selected as independent variables and the Cumulative % drug release in 1.5 h (DR1.5), Cumulative % drug release in 8 h (DR8), Cumulative % drug release in 24 h (DR24) and Floating lag time (FLT) were used as dependent variables. Results: CCD analysis results shows that predicted and experimental values for optimized formulation were found to be almost similar. Optimized amounts of Eudragit RSPO, HPMC K-100M, and NaHCO3 were 14.351 mg, 44.438 mg, and 10 mg, respectively, with the highest possible desirability value of 0.898. The experimental values at optimized preparation conditions were found to be DR1.5 is 30.68%, DR8 is 64.90%, DR24 is 96.54%, and FLT is 4.41 min. The release data from the optimized formulation were closely matched with the Korsmeyer-Peppas model and in vitro drug release studies indicated that the RG-GRF Tablet continuously releases the drug for 24 h in a controlled manner. Conclusion: Current research concludes that RG-GRF Tablets provide drug release for up to 24 h, and the derived central composite design can be used for forecasting the DR1.5, DR8 and DR24 as well. RG can also be made more bioavailable by extending the gastric residence time. Keywords: Gastro-retentive, Floating tablet, Central composite design, Repaglinide, Controlled release © 2023 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.2023v15i1.46493. Journal homepage: https://innovareacademics.in/journals/index.php/ijap INTRODUCTION Fast gastric emptying caused by conventional oral dosage forms reduces the bioavailability of many pharmacological compounds for which the stomach is the primary site of absorption [1] or proximal portions of the small intestine or points out a problem with absorption in the distal part of the intestine [2]. Controlled drug delivery systems with an extended residence time in the stomach can be used to improve the absorption as well as bioavailability of the drug. To extend the stomach retention duration [3] of a dosage form, many pharmaceutical strategies have been used. The Gastro- retentive Floating Drug Delivery System [4, 5] is an alternative approach to drug delivery that can improve the drug's continuous release over a longer period, in a controlled manner at the required absorption site, until the entire amount of the drug has been released from the dosage form [6]. Repaglinide (RG) is a new oral anti-diabetic drug of BCS-II in the Biopharmaceutical Classification System [7], used to treat type 2 diabetes. It has low oral bioavailability (56%), low aqueous solubility, and a short terminal elimination half-life (1 h) but is quickly and totally absorbed from the digestive tract [8, 9]. Because of its short plasma half-life and high dosing frequency, the immediate-release tablet is taken before each meal to maintain its therapeutic plasma levels. RG is a good candidate [10] for the development of a gastro- retentive dosage form because of its short duration of action, quick clearance, stability against enzymes, and most of its absorption takes place in the upper GIT (stomach). Repaglinide Gastro-retentive Floating tablet (RG-GRF Tablet) was used to improve the residence duration in the stomach [11] so that we can reduce the dosing frequency of the drug since this medication must be taken for an extended period to improve patient compliance [12, 13]. Central Composite Design [14] is an effective statistical and mathematical technique for investigating both the critical values at which the desired response would be achieved and the possible interactions between the independent and dependent variables were analyzed. In this study, we used the CCD to systematically examine the effects of various formulation factors on the drug release and buoyant characteristics of an RG-GRF Tablet. To achieve the desired result, the quantity of different excipients (HPMC-K 100M and Eudragit RSPO) and gas generating agent (NaHCO3) were chosen as independent variables, while the Cumulative % Drug Release in 1.5 H (DR1.5), Cumulative % Drug Release in 8 H (DR8), Cumulative % Drug Release in 24 H (DR24), and Floating Lag Time (FLT) were chosen as dependent variables and based on the findings of initial research carried out in our lab, these formulation variables ranges were selected. Our research's objective was to formulate an RG-GRF Tablet with a controlled drug release pattern of up to 24 h and Total Floating Time (TFL) of 24 h using different concentrations of Eudragit RSPO, HPMC K-100M and Sodium bicarbonate. MATERIALS AND METHODS Repaglinide was purchased from Yarrow Chem Products Mumbai. Hydroxypropyl methylcellulose (HPMC K-100M), polyvinylpyrrolidone (PVP K30) and eudragit RSPO were obtained from Colorcon Co., Ltd India. Anhydrous Lactose, Sodium bicarbonate, Microcrystalline Cellulose (MCC-101), Citric acid, Talc and Magnesium stearate were procured from SD Fine Ltd., Mumbai, and all other chemicals used were of analytical grade. Preparation of repaglinide solid dispersion (RG-SD) The solvent evaporation technique [13] was used to prepare RG-SD. RG and PVP K30 were precisely weighed in a 1:10 ratio. The mixture of RG and PVP K30 were added to the anhydrous ethanol. Using a water bath at 60 °C with vigorous stirring, the solvent was evaporated and formed a product. Then it was dried in a vacuum oven. The prepared solid dispersion was milled and dried out in a vacuum for 24 h, which is then subjected to pulverization and sieving. Preparation of repaglinide gastro-retentive floating tablet (RG- GRF tablet) Direct compression technology [15] was used for the preparation of RG-GRF Tablets. 22 mg RG-SD and matrix forming agent (Eudragit International Journal of Applied Pharmaceutics ISSN- 0975-7058 Vol 15, Issue 1, 2023