Size discrimination in rat and mouse gastric emptying

Shih Fan Jang, Beth A. Goins, William T. Phillips, Cristina Santoyo, Allison Rice-Ficht, Jason T. McConville

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Abstract

Objectives To investigate the relationship between particle size and gastric emptying in rodents using radiolabeled insoluble polymethyl methacrylate (PMMA) microcapsules/beads. Methods PMMA microcapsules (50-500 μm) and beads (0.5-3 mm) loaded with technetium-99 m diethylenetriamine pentaacetic acid (99mTc-DTPA) were administered to ICR mice or Sprague Dawley (SD) rats by oral gavage. Gamma scintiscans were acquired initially following administration and then at hourly intervals to 4 hours. Results Scintiscans revealed that the smallest PMMA microcapsules (50-100 μm) or beads (0.5-1 mm) were impeded in the stomach and emptied slower than large particles in both rodent species. In mice, no significant difference in gastric emptying was found with microcapsules between 100 and 300 μm in diameter (p = 0.25) and particles more than 300 μm could not be administered. In rats, capsules containing 0.5-3 mm beads were stuck to the esophagus (up to 1 hour), this was a limitation of dosing beads of this size because they cannot be suspended in a liquid media for oral gavage purposes. Beads with diameters of 2-3 mm stayed in the stomach for up to 4 hours. Conclusions The cut-off emptying size in ICR mice could not be determined, due to the limitation of current available dosing methods. The cut-off emptying size in SD rats was between 1.5 and 2 mm. Therefore, particles with a diameter greater than 2 mm should not be used for gastric emptying studies of intact particles in SD rats, as their emptying is retarded in the stomach.

Original languageEnglish (US)
Pages (from-to)107-124
Number of pages18
JournalBiopharmaceutics and Drug Disposition
Volume34
Issue number2
DOIs
StatePublished - Mar 1 2013

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Keywords

  • gamma scintigraphy
  • gastric emptying
  • microencapsulation
  • pyloric cut-off
  • surface polymerization

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

Jang, S. F., Goins, B. A., Phillips, W. T., Santoyo, C., Rice-Ficht, A., & McConville, J. T. (2013). Size discrimination in rat and mouse gastric emptying. Biopharmaceutics and Drug Disposition, 34(2), 107-124. https://doi.org/10.1002/bdd.1828