Research Article SURFACE RESPONSE METHODOLOGY FOR DEVELOPMENT AND OPTIMIZATION OF NAPROXEN SUSTAINED RELEASE TABLETS MOHD ABDUL HADI 1 *, MD AZHARUDDIN 1 , A SRINIVASA RAO 2 , VINAY UMESH RAO 3 , Y SIRISHA 1 1 *Dept of Pharmaceutics, Bhaskar Pharmacy College, Moinabad, R.R District, Hyderabad-500075, India., 2 Dept of Pharmacy Practice, Bhaskar Pharmacy College, Moinabad, R.R District, Hyderabad-500075, India., 3 Institute of Pharmaceutical Sciences, PJR Enclave, Madhavpuri hills, Chandanagar, Hyderabad. Email: hadi.lcp@gmail.com Received: 30 October2013,Revised and Accepted: 19November2013 ABSTRACT Objective: The current work focuses on the development and optimization of Naproxen 800mg sustained release tablets using surface response methodology. Methods: The drug release was controlled by formulating it into a sustained release tablet. The formulae was developed using various individual concentrations and viscosity grades of HPMC polymers for Naproxen SR tablets. The compatibility of polymers along with pure drug Naproxen was evaluated using FTIR and DSC studies. The tablets were prepared and Pre- and Post-compressional parameters, In-vitro dissolution testing, release rate kinetics and stability studies were evaluated. Results: The FT-IR and DSC spectras confirms the absence of chemical interaction between drug and polymers. All the Pre-compressional and Post- compressional parameters were found to be in limits. From the dissolution testing of all these formulations the low and high level of polymer concentrations which were within the range of Target product profile was determined. The design space as defined by the above experiments is within 21.3 to 22.8 range of the total polymer concentration. The data for stability studies revealed that no considerable differences in drug content and dissolution rates for a period of 6 months as per ICH guidelines. Conclusion: Based on the above results, a design space for all the three polymers was successfully developed within which when the tablets are fabricated, the target product profile will always be achieved. Keywords:Rheumatoid arthritis; Naproxen; Sustained release matrix system; Hydrophilic polymers. INTRODUCTION Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks flexible (synovial) joints. It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility if not adequately treated [1]. Naproxen is a naphthylpropionic acid derivative. It is the only NSAID presently marketed as a single enantiomer and it is a nonselective COX inhibitor. Naproxen has been proved to be effective in both experimental and clinical pain like rheumatoid arthritis, osteoarthritis, juvenile arthritis and acute gout without any serious cardiovascular or respiratory side effects [2-5]. The drug is lipid soluble, practically insoluble at low pH and freely soluble at high pH. One of the most important commonly used methods for controlling drug release is to form a matrix system with the help of hydrophilic, inert and hydrophobic polymers [6-12]. During the last two decades there has been remarkable increase in interest in sustained release drug delivery system. Such dosage forms are designed to release a drug at a predetermined rate by maintaining a constant drug level for a specific period of time with minimum side effects. There are several advantages of sustained release (SR) drug delivery over conventional dosage forms like improved patient compliance due to less frequent drug administration, reduction of fluctuations in steady state drug levels, maximum utilization of the drug, increased safety margin of potent drug, reduction in healthcare costs through improved therapy, shorter treatment period and less frequency of dosing [13-20]. The design of experiments (DOE) is an efficient procedure for planning experiments so that the data obtained can be analyzed to yield valid and objective conclusions. Whereas, the design space is that established range of process parameters and formulation attributes that have been demonstrated to provide assurance of quality. It forms the linkage between development and manufacturing design. Thus, Response surface methodology requires minimum experimentation and time proving to be more effective and cost-effective than the conventional methods of formulating sustained release dosage forms [20-23]. Matrix oral SR dosage forms of drugs are widely used to improve drug tolerance or to yield dosing regimen that is to easier to manage for patients. However, production of a SR dosage form that would maintain an effective plasma Naproxen concentration would improve patient compliance. The purpose of this thesis was to optimize a sustained release naproxen dosage form using various viscosity grades of hydrophilic polymers. MATERIALS AND METHODS Materials Naproxen was obtained as a gift sample from IPS Pharma training institute, Hyderabad. HPMC K4M, HPMC K15M and HPMC K100M were obtained from Astra Zeneca, Bangalore. Lactose, Microcrystalline cellulose (PH 102), PVP K30 and Magnesium stearate was purchased from Himedia chem. Lab. Mumbai. Aerozil was purchased from Sisco research laboratories Pvt. Ltd. Mumbai. All other materials used were of analytical grade. Experimental Methods Excipients compatibility study:FT-IR Studies: FT-IR studies were performed and the spectras were recorded in the wavelength region of 4000 to 400 cm -1 . The procedure consisted of dispersing a sample (drug, polymers and mixture of drug and polymers in KBr and compressing into discs by applying a compaction pressure 400 psi for 2 min in a KBr press. The pellet was placed in the light path and the respective spectrums were obtained. Differential Scanning Calorimeter (DSC): Differential Scanning Calorimeter (DSC) allows the fast Evaluation of possible Vol 7, Issue 1, 2014 ISSN - 0974-2441