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The purpose of the present study was to develop and characterize an oral controlled release drug delivery system for concomitant administration of diclofenac sodium (DS) and chondroitin sulfate (CS). A hydrophilic matrix-based tablet using different concentrations of hydroxypropylmethylcellulose (HPMC) was developed using wet granulation technique to contain 100 mg of DS and 400 mg of CS. Formulations prepared were evaluated for the release of DS and CS over a period of 9 hours in pH 6.8 phosphate buffer using United States Pharmacopeia (USP) type II dissolution apparatus. Along with usual physical properties, the dynamics of water uptake and erosion degree of tablet were also investigated. The in vitro drug release study revealed that HPMC K100CR at a concentration of 40% of the dosage form weight was able to control the simultaneous release of both DS and CS for 9 hours. The release of DS matched with the marketed CR tablet of DS with similarity factor (f2) above 50. Water uptake and erosion study of tablets indicated that swelling followed by erosion could be the mechanism of drug release. The in vitro release data of CS and DS followed Korsmeyer-Peppas and zero-order kinetics, respectively. In conclusion, the in vitro release profile and the mathematical models indicate that release of CS and DS can be effectively controlled from a single tablet using HPMC matrix system.