GASTROINTESTINAL TRANSIT AND ABSORPTION OF THEOPHYLLINE FROM A MULTIPARTICULATE CONTROLLED-RELEASE FORMULATION

The gastrointestinal transit and absorption of theophylline from a nov el multiparticulate controlled release formulation were investigated u nder 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 rele ase. Transit of the dosage form in the gastrointestinal tract, determi ned using a gamma scintigraphic method, revealed that the presence of food delayed the gastric emptying, but was without influence on the sm all intestinal transit time. The delay in gastric emptying was associa ted with a delay in drug absorption. However, the overall rate and ext ent of drug absorption were essentially unaffected by the presence of food. For both fed and fasted conditions, the rate of absorption whils t the pellets were in the stomach was slower than when the pellets wer e in the small intestine. The pellets were less well dispersed in the stomach than in the small intestine or colon. Moreover, whereas only 1 4% 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 ta ken up from the colon, which thus acts as a significant site of absorp tion.