Effect of simulated gastrointestinal changes on the in vitro release of theophylline from novel sustained-release matrix tablets with a protein carrier

Two cornpositionally similar sustained-release (SR) matrix tablets, T-2 and T-2-A, were developed with a protein carrier and theophylline as a model drug. Granules of T-2 were dried at room temperature (native protein carrier) while those of T-2-A were dried at 120°C for 30 min (denatured protein carrier). Changes in gastric emptying, motility and secretion of proteolytic enzymes were simulated, separately, by studying the in vitro release of theophylline under various conditions. Increases in the exposure time to simulated gastric fluid, agitation, and proteolytic enzymes content in the dissolution media resulted in more considerable increases in theophylline release profile from she T-2 tablet than from the T-2-A tablet. The two formulations were further evaluated pharmacokinetically in 5 mongrel dogs. Individual theophylline absorption profiles demonstrated that inter-dog variability was much less from the T-2-A tablet than from the T-2 tablet. The differences observed in the in vitro and in vivo performance of the T-2 and T-2-A tablets are most probably attributed to the differences in the protein carrier type of each formulation. Denatured and compressed protein carrier seems to be more stable to gastrointestinal (GI) changes than its native form.