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

• Published in: International journal of pharmaceutics Vol. 140; no. 2; pp. 229 - 235
• Main Authors: Abrahamsson, Bertil, Alpsten, Magne, Jonsson, Ulf E., Lundberg, P.J., Sandberg, Anders, Sundgren, Mats, Svenheden, Agneta, Tölli, Jukka
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 30.08.1996; Elsevier
• Subjects: Biological and medical sciences; Gamma scintigraphy; Gastrointestinal transit; General pharmacology; Medical sciences; Metoprolol; Pellets; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Gastrointestinal transit; Metoprolol; Gamma scintigraphy; Pellets; Drug; Transit time; Digestive system; Formulation; Gut; Oral administration; Dosage form; Gastric emptying; Colon; Pellet(dosage form)
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/0378-5173(96)04604-2

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.