Gastrointestinal transit and absorption of theophylline from a multiparticulate controlled release formulation

Abstract

The gastrointestinal transit and absorption of theophylline from a novel multiparticulate controlled release formulation were investigated under fed and fasted conditions. The drug pellets of high drug loading were prepared using an extrusion spheronisation technique, and coated with a methylcellulose-ethylcellulose mixture to control the drug release. Transit of the dosage form in the gastrointestinal tract, determined using a gamma scintigraphic method, revealed that the presence of food delayed the gastric emptying, but was without influence on the small intestinal transit time. The delay in gastric emptying was associated with a delay in drug absorption. However, the overall rate and extent of drug absorption were essentially unaffected by the presence of food. For both fed and fasted conditions, the rate of absorption whilst the pellets were in the stomach was slower than when the pellets were in the small intestine. The pellets were less well dispersed in the stomach than in the small intestine or colon. Moreover, whereas only 14% of drug was released in the stomach, 47% was released in the small intestine. It is interesting that the remaining 39% of the drug was taken up from the colon, which thus acts as a significant site of absorption.