920 KEY WORDS: Hydroxypropylmethylcellulose, Immediate release, In vitro kineticand slow release. * Author to whom correspondence should be addressed. E-mail: muhammadhanif14@yahoo.com Latin American Journal of Pharmacy (formerly Acta Farmacéutica Bonaerense) Lat. Am. J. Pharm. 33 (6): 920-7 (2014) Regular article Received: March 17, 2014 Revised version: April 12, 2014 Accepted: April 18, 2014 Formulation Development and Optimization of Flurbiprufen and Ranitidine Bilayer Tablet Designed by Central Composite Rotatable Design (CCRD) and Their In Vitro Kinetic Studies Muhammad HANIF 1,2 *, Usman ZIA 1 , Akhtar RASUL 1 , Shahid SHAH 2 , Nida NAZER 1 , Vesh CHAURASIYA 2 & Shahnila SATTAR 3 1 College of Pharmacy, GC University Faisalabad,Pakistan 2 Department of Pharmacy, Bahauddin Zakariya University,Multan ,Pakistan 3 Department of organic chemistry, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan. SUMMARY. Bilayer tablets of flurbiprofen SR and ranitidine IR was developed by using HPMC K4-M and colloidal silicon dioxide. Twenty formulations were planned by using design expert and micromeritic properties were analyzed for selection of six suitable formulations. Single punch machine was used for compression of bilayer tablets and physicochemical and quality control evaluation was performed success- fully. Weight variation, hardness, friability and disintegration time were evaluated by pharmacopeial pro- cedures. Release of ranitidine IR was studied for 60 min, while flurbiprofen SR was analysed for 24 h. In vitro kinetic studies like zero order, first order, Hixson-Crowell, and Weibull were applied to ranitidine IR formulation and flurbiprofen SR formulation was evaluated by zero order, first order, Higuchi, Korsmey- er-Peppas, Hixson-Crowell and Weibull. Regression values of a first order in IR and zero order in SR were found to more than 0.97 and Weibull model was used to explain the shape factor formulation. S1 for- mulation was considered as the best one and was selected for further in vivo studies. RESUMEN. Se desarrollaron comprimidos bicapa de flurbiprofeno SR y ranitidina IR mediante el uso de HPMC K4-M y dióxido de silicio coloidal. Veinte formulaciones fueron planeadas usando diseño experto y se analiza- ron las propiedades micromeríticas para la selección de seis formulaciones. Se utilizó una compresora simple pa- ra la obtención de los comprimidos bicapa y la evaluación de las propiedades físico-químicas y de control de ca- lidad fueron exitosas. La variación de peso, dureza, friabilidad y tiempo de desintegración fueron evaluados por procedimietnos farmacopeicos. La liberación de ranitidina IR se estudió durante 60 min y flurbiprofeno SR du- rante 24 h. Estudios cinéticos in vitro de orden cero, primer orden, Hixson-Crowell y Weibull fueron aplicados a la formulación de ranitidina IR., en tanto que la formulación de flurbiprofeno SR fue evaluada mediante estudios de orden cero, primer orden, Higuchi, Korsmeyer-Peppas, Hixson-Crowell y Weibull. Los valores de la regresión de primer orden en IR y de orden cero en SR resultaron superiores a 0.97 y el modelo de Weibull se usó para ex- plicar la formulación del factor de forma. La formulación S1 se consideró la mejor y fue seleccionada para poste- riores estudios in vivo. INTRODUCTION World health economists are mainly con- cerned about the cost effectiveness of the medicines by seeking the strategies to change the world of medicines of proven clinical effec- tiveness as well as cost effectiveness 1 . NSAIDs are the most widely prescribed drugs for the management of pain and inflammation. The prevalence of gastro duodenal ulcer is 15 to 30% in regular users of NSAIDs and it may de- velop in a week to months. H2 receptor antago- nists are very effective in reducing the risk of NSAID induce ulcer and also used when neces- sary to relieve NSAIDs related dyspepsia 2 . Flurbiprofen belongs to non-steroidal anti-in- flammatory drugs. It is a white or slightly yel- lowish crystalline powder slightly soluble in wa- ter at pH 7.0. The chemical name is 2-fluoro-α- methyl-1,1-biphenyl-4-acetic acid (Fig. 1). Ranitidine reversibly blocks the H 2 receptors and used in heart burn, peptic ulcer, and dys- pepsia. It is soluble in water having empirical ISSN 0326 2383 (printed ed.) ISSN 2362-3853 (on line ed.)