Design And Evaluation Of A Multiparticulate System For Chronotherapeutic Delivery Of Diclofenac Sodium
An oral controlled onset dosage form intended to approximate the chronobiology of rheumatoid arthritis is proposed for colonic targeting. The multiparticulate system comprising of nonpareil seeds coated with a mixture of Eudragit S-100 and L100 was designed for chronotherapeutic delivery of diclofenac sodium. The drug was loaded onto non-pareil seeds by powder layering technique using the conventional coating pan. Different coat weights of non-aqueous based Eudragit dispersions were applied onto the drug-loaded pellets using a pilot type spray gun. In vitro dissolution tests of the coated pellets were performed In different pH media following pH progression method for a period of 12 h. The in vitro dissolution tests showed that the release of diclofenac sodium from the coated pellets depended on the pH of the dissolution fluid and the coat weights applied. All the formulations exhibited an initial lag period characterized by limited dissolution (5.49% to 10.83%) followed by rapid release of the drug. The high ratio of drug solubility relative to the dosing amount promoted rapid release of the drug after the lag period. The release kinetics of diclofenac sodium from the coated pellets in pH 7.4 buffer fitted well Into Hixson-Crowell dissolution model.