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 proc ess 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 di ssolution of naproxen and Eudragit L 100-55 in alcohol USP followed by the addition of an aqueous solution containing a surfactant and deaggregating a gents. The mixture was stirred for a specified time period to obtain micros pheres, which were filtered and air-dried to a constant weight. The microsp heres 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 evalua te the main effects of homogenization time (X1), rate of water addition (X2 ), amount of polymer (X3), amount of precipitating solution (X4), concentra tion of electrolytes (X5), compression pressure (X6), and the concentration of lubricant (X7) on the rate of drug release. The response variable was c umulative percent of naproxen dissolved in 12, h in simulated intestinal fl uid with constraints on responses that included percent yield, hardness, th ickness, 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 X-1 + 3.51 X-2 + 3.84 X-3 - 3.80 X-4 - 2.46 X-5 - 2.90 X-6 - 3.91 X-7. The results showed that all the seven factors affected, with varying order, the release of na proxen from its compressed tablets.