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By: Hala M. Fadda

Hala Fadda - finalThe small intestine is the part of our gut where most nutrient and drug absorption takes place. Therefore, the time a modified release tablet or capsule spends in our small intestine will impact how much drug is available for absorption and could, ultimately, influence treatment efficacy. Capsule endoscopy (camera capsule) is a powerful tool for imaging the gut. It is similar in size to a vitamin capsule and has a lens and camera that capture images. The patient swallows the camera capsule with a glass of water, and then a video is generated as it transits through the gut. The capsule eventually passes out of the gut with a bowel movement. This is a sensitive diagnostic technique that is used in the investigation of gastrointestinal diseases, such as Crohn’s disease, celiac disease, and gut bleeding.

Capsule endoscopy can be utilized in pharmacokinetic studies to help us understand the variability in drug bioavailability observed with certain medicines or in certain patient populations. We applied this technique to investigate small intestinal transit times in different patient populations suffering from inflammatory bowel disease. Small intestinal transit times (SITT) are determined from the first duodenal image (as soon as the capsule empties from the stomach) to the first cecal image (as soon as the capsule leaves the ileocecal valve).

Snapshot images of our gut

Snapshot images of our gut

Our study published in AAPS PharmSciTech shows that patients with ulcerative colitis and active Crohn’s disease have longer SITT compared to non-inflammatory bowel disease patients. Both Crohn’s disease and ulcerative colitis are inflammatory bowel diseases that are associated with inflammation of the gut; dysmotility and prolonged transit times may explain nausea and vomiting, bloating, and visible abdominal distention in these patients. Crohn’s disease can affect any region of the gut, from mouth to anus, whereas ulcerative colitis only affects the colon and rectum. The prolonged SITT observed in ulcerative colitis patients is, therefore, particularly interesting and is likely to be attributable to the association between the motor activity of the small intestine and colon. SITT can play an important role in the clinical response for patients with inflammatory bowel disease to mesalamine delivery systems, which are indicated for the induction and maintenance of remission in ulcerative colitis. Information on transit times can aid in developing and selecting the most suitable drug delivery systems for Crohn’s and ulcerative colitis patients.

We have also shown that large variability exists in SITT of individuals with no identifiable gastrointestinal pathologies. SITT were found to range from 50 minutes to 460 minutes in a study examining the influence of sex and age on small intestinal transit times.  This variability could impact the rate and extent of drug absorption (bioavailability) and have clinical significance. As a next step, this variability also needs to be simulated in in vitro dissolution (drug release) testing for improving the prediction of drug release behavior in vivo (developing in vitro-in vivo correlations).

Drawing of the gastrointestinal tract is courtesy of the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), National Institute of Health

Hala Fadda, Ph.D., is Associate Professor of Pharmaceutics at Butler University. Her research focuses on characterization and simulation of the gastrointestinal and ocular environments to improve testing and development of site-specific drug delivery systems.