Gastro-intestinal transit of a multiple-unit formulation (metoprolol CR/ZOK) and a non-disintegrating tablet with the emphasis on colon

The main aim of the present study was to compare the transit through the entire gastro-intestinal channel of a membrane-coated, multiple-unit system containing metoprolol and a single-unit placebo tablet using gamma-scintigraphy. The two formulations were simultaneously administered, together with a breakfast (2800 kJ), to eight healthy male volunteers. The mean gastric emptying time for the pellets was 3.6 (range 1.5-5.0) h on average and the mean gastric emptying time for the tablet was 9.6 (range 3.3-(14-24)) h. This difference was statistically significant. The mean transit through the small intestine, 3.1 (range 1.5-5.7) h and 2.0 (range 1.0-3.3) h for the pellets and the tablet respectively, did not differ significantly between the formulations. The pellets had a longer residence time in the colon in all subjects compared with the tablet. The mean colon transit time was 28 (range 6.0-48) h on average for the pellets and 15 (range 3.8-26) h for the tablet. The tablet was expelled 26 (range 9.5-42)h after intake on average, whereas the pellets remained for a significantly longer time period (mean 35, range 10-55 h). The desired extended-release properties and metoprolol absorption was obtained throughout the entire gastrointestinal (GI) tract.