Pharmaceutical Research

, Volume 23, Issue 1, pp 165–176

Characterization of the Human Upper Gastrointestinal Contents Under Conditions Simulating Bioavailability/Bioequivalence Studies

  • Lida Kalantzi
  • Konstantinos Goumas
  • Vasilios Kalioras
  • Bertil Abrahamsson
  • Jennifer B. Dressman
  • Christos Reppas
Research Paper

Purpose

This study was conducted to compare the luminal composition of the upper gastrointestinal tract in the fasted and fed states in humans, with a view toward designing in vitro studies to explain/predict food effects on dosage form performance.

Methods

Twenty healthy human subjects received 250 mL water or 500 mL Ensure plus® (a complete nutrient drink) through a nasogastric tube and samples were aspirated from the gastric antrum or duodenum for a period up to 3.5 h, depending on location/fluid combination. Samples were analyzed for polyethylene glycol, pH, buffer capacity, osmolality, surface tension, pepsin, total carbohydrates, total protein content, and bile salts.

Results

Following Ensure plus® administration, gastric pH was elevated, buffer capacity ranged from 14 to 28 mmoL L−1 ΔpH−1 (vs. 7–18 mmol L−1 ΔpH−1), contents were hyperosmolar, gastric pepsin levels doubled, and surface tension was 30% lower than after administration of water. Post- and preprandial duodenal pH values were initially similar, but slowly decreased to 5.2 postprandially, whereas buffer capacity increased from 5.6 mmol L−1 ΔpH−1 (fasted) to 18–30 mmol L−1 ΔpH−1 (p< 0.05). Postprandial surface tension in the duodenum decreased by >30%, bile salt levels were two to four times higher, luminal contents were hyperosmotic, and the presence of peptides and sugars was confirmed.

Conclusions

This work shows that, in addition to already well characterized parameters (e.g., pH, and bile salt levels), significant differences in buffer capacity, surface tension, osmolality, and food components are observed pre-/postprandially. These differences should be reflected in test media to predict food effects on intralumenal performance of dosage forms.

Key Words

Ensure plus® fasted state fed state human gastric fluid human intestinal fluid 

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Lida Kalantzi
    • 1
  • Konstantinos Goumas
    • 2
  • Vasilios Kalioras
    • 2
  • Bertil Abrahamsson
    • 3
  • Jennifer B. Dressman
    • 4
  • Christos Reppas
    • 1
  1. 1.Laboratory of Biopharmaceutics and Pharmacokinetics, School of PharmacyUniversity of AthensZografouGreece
  2. 2.Red Cross Hospital of AthensAthensGreece
  3. 3.Preformulation and Biopharmaceutics DepartmentAstraZeneca R&DMölndalSweden
  4. 4.Department of Pharmaceutical TechnologyJW Goethe University of FrankfurtFrankfurtGermany

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