Naproxen-Eudragit microspheres: screening of process and formulation variables for the preparation of extended release tablets.

The objectives of the present study were to screen the formulation and process variables for the preparation of extended release naproxen tablets with Eudragit L100-55. The tablets were prepared by compression of microspheres that were obtained by a coprecipitation technique. The process involved dissolution of naproxen and Eudragit L 100-55 in alcohol USP followed by the addition of an aqueous solution containing a surfactant and deaggregating agents. The mixture was stirred for a specified time period to obtain microspheres, which were filtered and air-dried to a constant weight. The microspheres were then compressed to obtain plain tablets with a diameter of 12 mm. A 7-factor 12-run Plackett-Burman screening design was employed to evaluate the main effects of homogenization time (X1), rate of water addition (X2), amount of polymer (X3), amount of precipitating solution (X4), concentration of electrolytes (X5), compression pressure (X6), and the concentration of lubricant (X7) on the rate of drug release. The response variable was cumulative percent of naproxen dissolved in 12 h in simulated intestinal fluid with constraints on responses that included percent yield, hardness, thickness, and the angle of repose. Mathematical relationship for percent of naproxen dissolved in 12 h (Y5) with various factors yielded the following polynomial equation; Y5 (% dissolved in 12 h) = 95.48 + 0.53 X1 + 3.51 X2 + 3.84 X3 - 3.80 X4 - 2.46 X5 - 2.90 X6 - 3.91 X7. The results showed that all the seven factors affected, with varying order, the release of naproxen from its compressed tablets.