Impact of Ethyl Cellulose Ether Derivative (Ethocel) on the In Vitro and In Vivo Release of Nimesulide from Matrix Tablets

This research was carried out to investigate the effect of an ethyl cellulose ether derivative (Ethocel(R)) on the release of nimesulide from matrix tablets prepared by direct compression. Simultaneously it was evaluated the in vitro-in vivo relationships from the prepared tablets. Several parameters were studied including the effect of particle size of the polymer, drug to polymer ratio, in vitro release behaviour and the in vivo release profile. Different batches of nimesulide were prepared with Ethocel(R) 7 Premium and Ethocel(R) 7 Fine Particle Premium (7FP) with different drug to polymer ratios for each polymer by direct compression. In vitro release was studied using the USP method I (rotating basket method) in phosphate buffer (pH 7.4) at 37 degrees C +/- 0.5 degrees C using a rotational speed of 100 rpm. Samples were analyzed at predetermined time intervals by UV visible spectrophotometer. In vivo studies were carried out in rabbits. Analysis of plasma samples was conducted by HPLC. The in vitro dissolution studies showed that the particle size and the drug to polymer ratio markedly influenced the release profile. Different kinetic models were applied to the release data for each formulation. All the formulations followed non-Fickian anomalous release. A good level A in vitro-in vivo correlation was achieved with a coefficient of determination (r(2)) equal to 0.9418. The study showed that Ethocel(R) 7P and 7FP can successfully be used as a rate controlling agent for nimesulide controlled release matrix tablets.