Response surface methodology to obtain naproxen controlled release tabletsfrom its microspheres with Eudragit L100-55

Purpose: Naproxen CR tablets have been obtained from its microspheres prepa red by coprecipitation with Eudragit L100-55. The purpose of this work was to evaluate the main and interaction effects of deaggregating agent concent ration. (X-1), compression pressure. (X-2) and amount of precipitating wate r. (X-3) on naproxen release. A secondary purpose was to obtain an optimize d naproxen controlled release solid oral dosage form with a predictable 12 h drug release. Method: Eudragit L100-55 (10 g) was dissolved in 100 mL of ethyl alcohol, a nd 30 g of naproxen was dispersed in it with stirring. Purified water (100 mL, cooled to 4 degreesC) containing calcium chloride as a deaggregating ag ent was added to an alcoholic solution and homogenized. The mixture was fil tered to obtain microspheres. Drug content analysis was performed spectroph otometrically at 332 nm. Tablets were prepared by compressing microspheres containing 500 mg of naproxen after adding 1% magnesium stearate. Dissoluti on was performed by the USP specifications of naproxen tablets. A 3-factor 3-level Box-Behnken design was employed to get 15 experimental runs. The in dependent variables used were X-1, X-2 and X-3. The dependent variables wer e dissolution at different time points with constraints on yield value and angle of repose of the microspheres, and hardness and thickness of the tabl ets. The dissolution constraints were placed such that the naproxen is rele ased for 12 h by Higuchi's square root of time kinetics. Results: The mathematical relationship obtained between X-1, X-2, X-3 and t he cumulative per cent of naproxen dissolved in 12 h with various constrain ts. (Y-5) was Y-5 = 2.39 - 1.13X(1) - 4.84X(2) - 2.12X(3) - 2.26X(1)X(2) - 0.5X(1)X(3) - 0.4X(2)X(3) + 2.4X(1)(2) - 0.4X(2)(2) (R-2 = 0.9). The equati on shows that X-1, X-2 and X-3 affected the release inversely, and the most significant interaction was between X-1 and X-2. Y-5 has been maximized fo r optimization of naproxen release. Conclusions: Controlled release tablets of naproxen with predictable drug r elease characteristics were obtained by compressing its microspheres with E udragit L100-55.