Formulation and evaluation of sustained release bilayer tablets of naproxen and tizanidine

Synergistic effects of drugs give new prospects for the pharmaceutical scientists. Bilayer tablet of two synergistic drugs like naproxen and tizanidine was prepared by taking naproxen as sustained release layer and tizanidine as immediate release layer. Wet granulation method was used by using polymer HPMC K15-M and HPMC K100-M in 1:1 ratio for sustained release formulation and simple direct compression method was established for tizanidine powder blend. About 14 formulations were planned by using Design expert and flow properties were studied for granules and powder blend. Seven formulations among 14 were selected due to their excellent and good flow properties. Single punch ma-chine was used for compression of bilayer tablet and tablets were evaluated for post compression parameters like weight variation, hardness, friability, and disintegration time by recommended procedures. Tizanidine containing IR layer studied for 45 min. Whereas naproxen release from SR layer was studied for 12 h. Phosphate buffer pH 7.4 was used for the dissolution studies of naproxen and 0.1 N HCl at pH 1.2 for tizanidine layer. All physicochemical tests like weight variation ± 5%, friability was less than 1%, disintegration time was less than 5 min for immediate release and more than 4 h for sustained release layer. Tizanidine IR and naproxen SR released the drug more than 80% in 15 min and 12 h, respectively. In vitro kinetic studies like zero order, first order, Hixson-Crowell, and Weibull was conducted for IR tizanidine layer; zero order, first order, Higuchi, Korsmeyer-Peppas, Hixson-Crowell, and Weibull models were applied for SR naproxen layer. Regression values for first order in immediate release and zero order in SR were found to more than 0.97.