Formulation Development and Optimization of Febuxostat Tablets by Direct Compression Method UZMA ASIF, ASIF K. SHERWANI, NAHEED AKHTAR Department of Biochemistry, University of Karachi, Sindh, Pakistan MUHAMMAD HARRIS SHOAIB Department of Pharmaceutics, University of Karachi, Sindh, Pakistan MUHAMMAD HANIF Department of Pharmacy, Bahauddin Zakariya University Multan MUHAMMAD IMRAN QADIR Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University Multan MUHAMMAD ZAMAN Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan Correspondence to: Muhammad Hanif; e-mail: muhammadhanif14@yahoo.com. Received: December 31, 2014 Accepted: March 19, 2015 ABSTRACT: The aim of this study was to develop a simple and cost-effective Febuxostat film coated tablet formulation by the direct compression method. To obtain the best optimized product, nine different formulations were developed using a central composite rotatable design. Avicel PH-102, Magnesium stearate, and croscarmellose sodium were taken as independent variables. Micromeritic properties of powder blend showed excellent flow properties and were within USP limits. Tablets were compressed and before coating the core was tested for weight variations, hardness, thickness, friability disintegration, and dissolution. Tablets were film coated using hydroxypropyl methylcellulose 5cps, titanium dioxide, polyethylene glycol, and Instacoat blue, and again tested for the weight variations, assay, and single point dissolution. Three different dissolution media, i.e., 0.1 N HCl (pH 1.2) and phosphate buffer pH 4.5 and 6.8, were used for calculating the percentage release of Febuxostat and their release pattern was compared with an innovator brand by using the model-independent methods such as similarity (f 2 ), dissimilarity (f 1 ), and model-dependent methods such as first-order, Hixson Crowell, and Weibull methods. The results revealed that Trial-06 showed the maximum similarity, i.e., 81.18, 75.15, and 67.19 in three different pH dissolution media. Dissimilarity factor was also comparable in Trial 06, i.e., 5.21, 11.27, and 6.01 at pH 1.2, 4.5, and 6.8, respectively. Model-dependent approaches showed the maximum r 2 values for Trial 06, i.e., greater than 0.900 for all models in the above-mentioned pH, whereas the overall release kinetics followed the Weibull model. Selected formulation was kept at 40 ± 5°C and 75 ± 2% relative humidity for accelerated stability studies, and no specific change was observed. C  2015 Wiley Periodicals, Inc. Adv Polym Technol 2015, 00, 21536; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.21536 KEY WORDS: Central composite rotatable design, Calculations, Febuxostat, UV-vis spectroscopy, Water-soluble polymers and calculations Introduction F ebuxostat is a nonpurine selective inhibitor of xanthine ox- idase. It works by noncompetitively blocking the channel leading to the active site on xanthine oxidase. Xanthine oxidase is needed to successively oxidize both hypoxanthine and xan- thine to uric acid. Hence, Febuxostat inhibits xanthine oxidase, therefore reducing production of uric acid. Most common dis- ease of high uric acid level is gout. It is a kind of arthritis that occurs when uric acid built up in the joint. Direct compression is a process by which tablets are com- pressed directly from the mixture of drug and excipients, without any preliminary treatment. 1 A simple formulation composition could be an active ingredient, a diluent, and a Advances in Polymer Technology, Vol. 00, No. 0, 2015, DOI 10.1002/adv.21536 C  2015 Wiley Periodicals, Inc. 21536 (1 of 7)