Transit of pharmaceutical dosage forms through the small intestine.

Abstract

SUMMARY The gastrointestinal transit of pharmaceutical dosage forms has been measured in 201 studies in normal subjects using gamma scintigraphy. Solutions, small pellets, and single units (matrix tablets and osmotic pumps) were administered with different amounts of food in the stomach, ranging from fasted state to heavy breakfast. Gastric emptying was hiffected by the nature of the dosage form and the presence of food in the stomach. Solutions and pellets were emptied even when the stomach was in the digestive mode, while single units were retained for long periods of time, depending on the size of the meal. In contrast, measured intestinal transit times were independent of the dosage form and fed state. The small intestinal transit time of about three hours (mean ± 1 h SEM) has implications for the design of dosage forms for the sustained release of drugs in specific positions in the gastrointestinal tract.The main site for the absorption of drugs in man is considered to be the small intestine, with its high effective surface area.' Little, if any, drug absorption occurs from the stomach, although some drugs are thought to be absorbed to a limited extent from the large intestine. As a general rule, therefore, drugs should be formulated so that they can be largely absorbed from the small intestine.Ho, Higuchi, and colleagues2 3 have introduced the concept of the 'reserve length' for drug absorption. This is defined as the anatomical length over which absorption of drug can occur, less the length at which absorption is complete. The reserve length is dependent on physiological factors, however, such as bulk flow rate, spreading of the dosage form in the small intestine and the permeability of the drug through the intestinal mucosa.In the pharmaceutical field, the length of time a dosage form can remain in the small intestine tends to have been overestimated4; particularly when consideration is given to controlled release systems designed to provide 24 hour dosage. In some cases insufficient attention has been paid to the influence of gastric emptying, or to the implications of the studies on the nature and function of the migrating myoelectric complex,5 and the consequent differ-

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

“…Despite the reasonably constant small intestinal transit time (cfr. supra: Scintigraphy), the food or drug matrix spends a considerable time at the ileocecal junction, which functions mechanistically as a valve allowing fecal material to become more concentrated before transfer to the colon (Davis et al, 1986). For time-dependent colonic drug delivery systems, which will release drug after a predetermined lag time, movement through this junction can be a significant variable (Jose et al, 2009; a b c Kinget et al, 1998;Pišlar et al, 2015;Wilson, 2010).…”

Theophylline‐terbutaline, a steady state study on possible pharmacokinetic interactions with special reference to chronopharmacokinetic aspects.

“…Food has been shown (Nyberg, 1984) to reduce the bioavailability of terbutaline and as the evening dose was taken only 2 h after intake of supper, when the stomach still should not be quite empty (Davis et al, 1986), this could influence the extent of absorption especially with a sustained-release preparation. A decreased gut motility, during the night, could also reduce the absorption of terbutaline.…”

In vitro Bioequivalence Studies in Tablet Formulation Containing 625 mg of Colesevelam Hydrochlorides

“…In addition, results of the kinetic studies shown that maximum binding to bile acids achieved in 15-30 min. When taken tablets with a meal, it takes much longer than 30 min to pass through the intestine [14]. Therefore, the tablets perform maximum binding pass through the intestine.…”