The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targeted site for both locally and systemically acting drug products. Previous magnetic resonance imaging (MRI) studies offered novel insights on GIT liquid distribution in fasted humans in the stomach and small intestine, and showed that freely mobile liquid in the intestine collects in fairly distinct regions or "pockets". Based on this previous pilot data, we hypothesized that (1) it is possible to quantify the time course of the volume and number of liquid pockets in the undisturbed colon of fasted healthy humans following ingestion of 240 mL, using noninvasive MRI methods; (2) the amount of freely mobile water in the fasted human colon is of the order of only a few milliliters. Twelve healthy volunteers fasted overnight and underwent fasted abdominal MRI scans before drinking 240 mL (∼8 fluid ounces) of water. After ingesting the water they were scanned at frequent intervals for 2 h. The images were processed to quantify freely mobile water in the total and regional colon: ascending, transverse, and descending. The fasted colon contained (mean ± SEM) 11 ± 5 pockets of resting liquid with a total volume of 2 ± 1 mL (average). The colonic fluid peaked at 7 ± 4 mL 30 min after the water drink. This peak fluid was distributed in 17 ± 7 separate liquid pockets in the colon. The regional analysis showed that pockets of free fluid were found primarily in the ascending colon. The interindividual variability was very high; the subjects showed a range of number of colonic fluid pockets from 0 to 89 and total colonic freely mobile fluid volume from 0 to 49 mL. This is the first study measuring the time course of the number, regional location, and volume of pockets of freely mobile liquid in the undisturbed colon of fasted humans after ingestion of a glass of water. Novel insights into the colonic fluid environment will be particularly relevant to improve our understanding and design of the in vivo performance of controlled release formulations targeted to the colon. The in vivo quantitative information presented here can be input into physiologically based mechanistic models of dissolution and absorption, and can be used in the design and set up of novel in vitro performance tools predictive of the in vivo environment.

Background: functional gastrointestinal disorders (FGID) are common conditions in children and adults, often associated with abnormalities of whole gut transit. Currently, transit tests can be performed using several imaging methods, including tracking of radiopaque markers, gamma scintigraphy with the use of radioisotopes, magnetic tracking methods, tracking of movement of wireless motility capsules, and emerging magnetic resonance imaging (MRI) approaches. Objectives: to review recent literature on diagnostic imaging techniques used to investigate whole gut transit in FGIDs. Methods: a systematic review was carried out. The different techniques are described briefly, with particular emphasis on contemporary literature and new developments, particularly in the field of MRI. Conclusions: emerging MRI capsule marker methods are promising new tools to study whole gut transit in FGIDs.Small intestinal bacterial overgrowth (SIBO) is another common disorder of the gastrointestinal tract. It reflects excess presence of bacteria in the small bowel, and recent studies suggest SIBO can be associated with altered gut transit [6].Constipation can be caused by slow transit of chyme within the colon. Different factors can contribute to this, including diet, lifestyle and medications [7]. Constipation can also signal the presence of other underlying disorders such as diabetes, coeliac disease and cancer [8].A recent review estimated the average prevalence of constipation at 16% worldwide [9]. In the United States, the number of hospital emergency visits linked to constipation increased by 41.5% between 2006 and 2011 [10]. Constipation is thought to be twice as common in women than in men [9]. Women at the postpartum stage (several weeks after pregnancy) are often affected by the condition, with up to 25% of women reporting the incidence of constipation [11]. Constipation rates tend to be substantially higher in the elderly population and reach up to 50-75%.Most cases of constipation are caused by one of three general mechanisms: disordered and obstructed defecation caused primarily by impaired rectal evacuation, irritable bowel syndrome with constipation, and slow transit constipation [12]. These mechanisms differ substantially, even though the general symptoms of constipation appear very similar. Proper treatment in each case calls for a patient-specific differential diagnosis. This diagnosis remains challenging and about half of all patients who complain of constipation remain unsatisfied with the treatment they receive [12].Slow transit constipation, a reduced intestine motility caused by abnormalities of the enteric nerves, accounts for 15-30% of all constipated patients, with up to 37% of constipated women affected [13].Functional constipation in childhood is very common. Its prevalence has been estimated to be 14%, forming approximately 3% of all hospital paediatric referrals [14][15][16][17][18]. In the majority of paediatric cases, constipation is not linked to specific clinical disorders but rather caused by changes i...