Effect of complexation with Phenobarbital on the Biologic Availability of Theophylline from Three Tablet Formulations

Abstract

A study was conducted to test the hypothesis that clinical differences occurring after the administration of theophylline, phenobarbital and ephedrine tablets of different manufacturers were due not only, to formulation factors but also to complexation between theophylline and phenobarbital A complex of phenobarbital with theophylline had a slower dissolution in three dissolution media than theophylline. The significance of this dissolution behavior was demonstrated in humans as higher serum levels of theophylline were measured after the oral administration of theophylline than upon the administration of the complex. Three tablet formulations containing theophylline, ephedrine and phenobarbital possessed different dissolution profiles in simulated gastric fluid. For the three tablet formulations tested in nine humans, the relationship of serum level of theophylline and time correlated with the dissolution profiles. This study indicates that bioavailability may be influenced by complexation or interaction between two drugs in a tablet.