Analysis of small intestinal transit and colon arrival times of non-disintegrating tablets administered in the fasted state

• Published in: European journal of pharmaceutical sciences Vol. 75; pp. 131 - 141
• Main Authors: Pišlar, Mitja, Brelih, Hana, Mrhar, Aleš, Bogataj, Marija
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.07.2015
• Subjects: Administration, Oral; Colon - physiology; Colon arrival; Fasting - physiology; Food-Drug Interactions; Gastric Emptying; Gastrointestinal Transit; Humans; Ileocecal junction residence; Intestine, Small - physiology; Non-disintegrating tablet; Post-dose meal intake; Small intestinal transit; Tablets - pharmacokinetics; Small intestinal transit; Ileocecal junction residence; Gastric emptying; Post-dose meal intake; Non-disintegrating tablet; Colon arrival
• DOI: 10.1016/j.ejps.2015.03.001
• ISSN: 0928-0987; 1879-0720

[Display omitted] In this study individual data on tablet gastrointestinal transit times (i.e. gastric emptying, small intestinal transit, ileocecal junction residence, and colon arrival times) were obtained from literature in order to present and analyze their distributions and relationships. The influence of the time of food intake after tablet administration in fasted state on gastrointestinal transit times was additionally evaluated. There were 114 measurements from subjects who received the first meal at 4h after tablet administration. Approximately 32% of the tablets arrived into the colon before the meal intake at 4h. An evident increase in the frequency of colon arrival of tablets within 40min after the meal intake at 4h post-dose was observed, where approximately 39% of all tablets arrived into the colon. This is in accordance with findings described in literature where a meal ingested several hours post-dose accelerates tablet transit through the terminal ileum and shortens the transit through the small intestine. The median (min, max) of gastric emptying, small intestinal transit, and colon arrival times in the group where the first meal intake was at 4h post-dose is 35 (0,192), 215 (60,544), and 254 (117,604) minutes, respectively. The dependence of colon arrival times on gastric emptying times was described by the nonparametric regression curve, and compared with the presumed interval of colon arrival times, calculated by summation of observed gastric emptying times and frequently cited small intestinal transit time interval, i.e. 3–4h. For shorter gastric emptying times the trend of colon arrival times was within the presumed interval. At short gastric emptying times many observation points are also within the presumed interval since this interval coincides with short period after meal intake at 4h post-dose. Additionally, in numerous occasions relatively long ileocecal junction residence times were obtained, which may be important information from the point of view of drug absorption. The findings of gastrointestinal transit times are important and should be taken into consideration when predicting the in vivo performance of dosage forms after oral administration.