Meal-Induced Acceleration of Tablet Transit Through the Human Small Intestine

PurposeThe transit of dosage forms through the small intestine is considered to be constant at around 3 h, and unaffected by the presence of food. Here we address this assumption and examine how the timing of tablet and food administration can influence small intestine transit time.MethodsA non-disintegrating, radiolabelled tablet was given to ten healthy volunteers in a three-way crossover study using three different feeding regimens (1) fasted (tablet administered on an empty stomach and food withheld for four hours) (2) fed (tablet administered after food) and (3) pre-feed (tablet administered 45 min before food). Tablet transit through the gastrointestinal tract was followed using gamma scintigraphy.ResultsThe small intestinal transit times of tablets after fasted and fed dosing regimens were similar, median 204 and 210 min respectively. With the pre-feed dose, small intestinal transit time was significantly shorter than in the fasted or fed state at 141 min. With this dosing regimen, in six of the volunteers tablets were in the upper small intestine when food arrived and these had a median small intestinal transit time of 100 min.ConclusionsThe timing of food ingestion has a clear effect on small intestinal transit of single-unit formulations and this has implications for drug bioavailability.

[1]  J. Barone,et al.  Cisapride: A Gastrointestinal Prokinetic Drug , 1994, The Annals of pharmacotherapy.

[2]  A. Basit,et al.  Interplay Between Intestinal pH, Transit Time and Feed Status on the In Vivo Performance of pH Responsive Ileo-Colonic Release Systems , 2008, Pharmaceutical Research.

[3]  J. Meyer,et al.  Inhibition of gastric emptying by glucose depends on length of intestine exposed to nutrient. , 1989, The American journal of physiology.

[4]  C. Matuchansky,et al.  Effects of Cholecystokinin and Metoclopramide on Jejunal Movements of Water and Electrolytes and on Transit Time of Luminal Fluid in Man , 1972, European journal of clinical investigation.

[5]  F. Podczeck,et al.  Determination of the gastric emptying of solid dosage forms using gamma-scintigraphy: a problem of image timing and mathematical analysis , 1999, European Journal of Nuclear Medicine.

[6]  P. Fleckenstein,et al.  Migrating electrical spike activity in the fasting human small intestine , 1978, The American Journal of Digestive Diseases.

[7]  J. Hardy,et al.  The effect of eating on transit through the small intestine. , 1989, Nuclear medicine communications.

[8]  A. Basit,et al.  Impact of formulation excipients on human intestinal transit , 2006, The Journal of pharmacy and pharmacology.

[9]  E. J. McCoy,et al.  Effect of feeding on electrical activity of dog's small intestine. , 1968, The American journal of physiology.

[10]  A. Parr,et al.  Gastrointestinal Behavior of Orally Administered Radiolabeled Erythromycin Pellets in Man as Determined by Gamma Scintigraphy , 1990, Journal of clinical pharmacology.

[11]  A. Parr,et al.  Effect of Sodium Acid Pyrophosphate on Ranitidine Bioavailability and Gastrointestinal Transit Time , 1993, Pharmaceutical Research.

[12]  J. Reynolds Prokinetic agents: a key in the future of gastroenterology. , 1989, Gastroenterology clinics of North America.

[13]  A. Basit,et al.  An investigation into the in vivo performance variability of pH responsive polymers for ileo-colonic drug delivery using gamma scintigraphy in humans. , 2006, Journal of pharmaceutical sciences.

[14]  L Bueno,et al.  Rate of flow of digesta and electrical activity of the small intestine in dogs and sheep. , 1975, The Journal of physiology.

[15]  A. Basit,et al.  A comparative in vitro assessment of the drug release performance of pH-responsive polymers for ileo-colonic delivery. , 2006, International journal of pharmaceutics.

[16]  I. Wilding,et al.  The effects of pharmaceutical excipients on small intestinal transit. , 1995, British journal of clinical pharmacology.

[17]  D. Taylor,et al.  On the intestinal transit of a single non-disintegrating object , 1984 .

[18]  N. Hosten,et al.  Intestinal fluid volumes and transit of dosage forms as assessed by magnetic resonance imaging , 2005, Alimentary pharmacology & therapeutics.

[19]  P. Fairclough,et al.  Erythromycin and the gut. , 1992, Gut.

[20]  I. Wilding,et al.  The Effect of Oleic Acid on the Human Ileal Brake and Its Implications for Small Intestinal Transit of Tablet Formulations , 2004, Pharmaceutical Research.

[21]  T. Borody,et al.  Human interdigestive motility: variations in patterns from esophagus to colon. , 1986, Gastroenterology.

[22]  S. Davis,et al.  Alimentary tract andpancreas Transit ofpharmaceutical dosage forms through the , 1986 .

[23]  K. Ofori-Kwakye,et al.  Gamma scintigraphic evaluation of film-coated tablets intended for colonic or biphasic release. , 2004, International journal of pharmaceutics.

[24]  I. Wilding,et al.  The Effect of Different Concentrations of Mannitol in Solution on Small Intestinal Transit: Implications for Drug Absorption , 1995, Pharmaceutical Research.

[25]  A. Basit,et al.  A new concept in colonic drug targeting: a combined pH‐responsive and bacterially‐triggered drug delivery technology , 2008, Alimentary pharmacology & therapeutics.

[26]  Martti Marvola,et al.  Neutron activation based gamma scintigraphic evaluation of enteric-coated capsules for local treatment in colon. , 2008, International journal of pharmaceutics.

[27]  W. Domschke,et al.  Human intestinal motor activity and transport: effects of a synthetic opiate. , 1986, Gastroenterology.

[28]  A. Zinsmeister,et al.  Relationship of motility to flow of contents in the human small intestine. , 1982, Gastroenterology.

[29]  Jm Newton,et al.  Comparative gastrointestinal transit of pellet systems of varying density , 1995 .

[30]  C F Code,et al.  The interdigestive myo‐electric complex of the stomach and small bowel of dogs. , 1975, The Journal of physiology.

[31]  Abdul W. Basit,et al.  Concentration-Dependent Effects of Polyethylene Glycol 400 on Gastrointestinal Transit and Drug Absorption , 2003, Pharmaceutical Research.