Development of a transmucosal technique for erythromycin delivery to treat gastroparesis

Ryan Mclemore, Brian Lunt, Sarah Salameh, John K. Dibaise, Michael D. Crowell, Brent L. Vernon

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Gastroparesis is a serious condition that limits meal or medication emptying from the stomach, resulting in a variety of symptoms, altered nutrition, and inconsistent medication delivery. Our aim was to develop a transmucosal system to deliver erythromycin (EM), a gastric prokinetic agent, to bypass intestinal absorption. Humans and Sprague-Dawley rats were given EM by injection, gavage, or transmucosal gel with or without permeation enhancers. Pharmacokinetics were compared between subjects and across different delivery modalities. Drug concentrations in blood were measured using a bioassay. Design of Experiment techniques were used to optimize transmucosal antibiotic delivery in the Sprague-Dawley Model. Finally, we examined the scale-up of transmucosal delivery to human patients. Transmucosal delivery of EM increased with addition of ursodeoxycholate. While EM release from gels with ursodeoxycholate was significant, it was less than by injection. Scale-up to a human model indicated that delivery of EM using this transmucosal delivery system is insufficient for clinical need. The transport of EM seems limited by its solubility in water and thickness of the epithelial cell layers. Providing successful transmucosal delivery of EM and similar molecules to humans will require more aggressive techniques to disrupt the cellular layer, or pro-drug strategies to increase lipid solubility.

Original languageEnglish (US)
Pages (from-to)2905-2913
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume99
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Bioassay
  • Carbopol/carbomer
  • Oral (buccal) mucosa
  • Permeation enhancer
  • Pharmacokinetics
  • Sprague-dawley rat

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Mclemore, R., Lunt, B., Salameh, S., Dibaise, J. K., Crowell, M. D., & Vernon, B. L. (2010). Development of a transmucosal technique for erythromycin delivery to treat gastroparesis. Journal of Pharmaceutical Sciences, 99(6), 2905-2913. https://doi.org/10.1002/jps.22037