Sustained-release Theophylline Matrix Tablet Using Hydrophilic Polymers: Effects of Agitation Rates and pH on Release Kinetics

Abstract

Background and Objective: Modified-release tablet of theophylline that can increase its usefulness despite narrow therapeutic index and short half-life, is being formulated. However, the rate and extent of release of a sustained-release delivery system can be affected by some factors. This work is aimed at investigating the effect of agitation rates and pH of dissolution medium on release kinetics of sustained-release theophylline tablet formulated using hydrophilic polymers. Materials and Methods: Theophylline granules was formulated using 3 polymers (HPMC, SCMC and Sodium alginate) to form 3 batches of granule by wet granulation method, using 95% ethanol. The granules compacted to batches of sustained-release matrix tablets. The tablet batches were characterized for tablet properties, and dissolution studies carried out using simulated gastric and intestinal fluid separately at different agitation rates. The data from dissolution studies were subsequently fitted into 4 drug release kinetics models. Results: The swelling of the 3 polymers over time was noteworthy, although there was no significant difference between them. The release kinetic followed the Higuchi model and zero-order releasing more than 90% over 8 hours period, with t10 and t90 released at 14 minutes and 6.8 hours respectively. The mechanical properties of the tablets were within the acceptable limit. Conclusion: The agitation rate and pH of the medium had no significant effect on the release of the theophylline from the batches of matrix tablets except in the case of F1 which showed a marginally significant effect.