Formulation, characterization and comparative in vitro in vivo evaluation of sustained release theophylline tablets

The following study involves formulation and evaluation of simple highly drug loaded matrix tablets of theophylline anhydrous (THF) containing ethylcellulose (EC) polymer as a release retardant at low concentrations (1- 9 %w/w) using wet granulation technique. An optimum formula was chosen on the basis of tablet physical properties and in vitro drug release. A kinetic study on theophylline release from selected matrix formula was established including zero order, first order, Higuchi, Hixson-Crowell and Korsmeyer-peppas kinetic models. The drug release was found to be non Fickian (n=0.54) due to both tablet diffusion and matrix erosion. The effects of certain formulation variables on drug release rate such as formulation technique, tablet geometrical shape and granule size were studied. The results have shown significantly different dissolution rates in case of applying one of the first two variables only. Finally, a comparative in vitro in vivo study was done between the selected formula and two theophylline sustained release (SR) dosage forms commercially available in the Egyptian market. The formulated tablets have shown the slowest release rate (86.68% after 8h) compared to the other two products of Quibron®-T/SR tablets and Theo SR® 300 mg capsules which have released 100% of their drug content after that time. According to the in vivo absorption profile, a significant difference in the means of C_max, T_max, t_1/2 and MRT was detected between the innovator and the two reference preparations. Such data provides strong evidence that the formulated THF tablets have better therapeutic sustaining effects than the two market products.