Pak. J. Pharm. Sci., Vol.24, No.2, April 2011, pp.183-192 183 INVESTIGATING THE IN VITRO DRUG RELEASE KINETICS FROM CONTROLLED RELEASE DICLOFENAC POTASSIUM-ETHOCEL MATRIX TABLETS AND THE INFLUENCE OF CO-EXCIPIENTS ON DRUG RELEASE PATTERNS SHEFAAT ULLAH SHAH, KIFAYAT ULLAH SHAH, ASIMUR REHMAN AND GUL MAJID KHAN* Drug Delivery Research center, Department of Pharmaceutics, Faculty of Pharmacy, Gomal University, Dera Ismail Khan (KPK), Pakistan ABSTRACT The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f 2 and dissimilarity factor f 1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical / kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especially at D:P ratios of 10:03 which lead towards the achievement of zero or near zero order release kinetics. Keywords: Diclofenac Potassium, Ethocel Standard Premium, Ethocel Standard FP Premium, controlled release tablets, release pattern and kinetics, influence of co-excipients. INTRODUCTION NSAID’s (Non steroidal anti-inflammatory drugs) are the drugs of choice in rheumatoid arthritis and osteoarthritis but their long therapy can cause a number of serious GIT disturbances like ulcers of esophagus, stomach and duodenum, leading to perforation, obstruction and severe bleeding (Dhikav et al., 2002). Diclofenac potassium is a derivative of benzene acetic acid. It is used as non- steroidal analgesic, antipyretic and anti-inflammatory drug. It is widely used for the relief of severe and moderate pain, osteoarthritis and rheumatoid arthritis (Diclofenac Potassium, 2009). In recent years, sustained release and controlled release delivery systems have achieved a great advancement in the world of medicine. In controlled delivery systems polymers are used to control the release rate of drug into the systemic circulation from the site of absorption and are used mainly in oral preparations such as capsules and tablets. These polymers in particle form combine with the drug particles and thus the release rate of drug from its moiety or matrix tablets is controlled in a constant manner for a specific period of time either preferably up to 24 hours. The controlled release drug delivery system is concerned with the maintenance of drug plasma level in an optimum range so as to reduce the toxicity (Vert et al., 1991). In controlled release dosage forms, the drug release rate from the tablet is influenced by different factors which are directly related to both physical and chemical properties of the drug and also to its dosage form. Mostly these factors are associated with the polymers used in the formulations and show a tremendous influence in the release of drug from the polymeric tablets. These factors include the amount of polymer used, its molecular weight, concentration and the particle size but the most important factors out of these are the concentration of polymer and the drug to polymer ratio which increases the release rate of drug from cellulose matrices (Ford et al., 1985, Mitchell et al., 1993). Ethyl cellulose ethers are widely used in controlled release preparations. In order to control the release rate of the drug, it is uniformly mixed with the drug or used in coating a tablet, particles and granules. It is also used in bitter drug formulations so as to mask the bitter taste for compliance. Ethyl cellulose ether derivatives contain different derivatives of which Ethocel standard premium and Ethocel standard FP premium are the most interesting ones and are used in many oral and other formulations to control the release rate (Khan and Median, 2007). MATERIALS AND METHODS Mono basic potassium phosphate, CMC, Starch and NaOH (Merck, Germany), Diclofenac Potassium (Leeds Pharma, Islamabad), Lactose and Magnesium stearate *Corresponding author: e-mail: gmkhan@gu.edu.pk