Animal models for predicting potency of oral sustained-release adhesive microspheres in humans

Naoki Nagahara, Yohko Akiyama, Kazutaka Higaki, Toshikiro Kimura

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The sustained-release (SR) adhesive microspheres successfully improved the absorption of furosemide, of which the absorption is limited to the upper small intestine, after oral administration to humans based on the adhesion to the gastric mucosa in our previous study. To develop a new drug using SR-adhesive microspheres, however, some adequate animal models should be needed to predict the potency of the formulation in humans. To find out an adequate animal model, the effect of the SR-adhesive microspheres on furosemide absorption was investigated in rats, dogs and monkeys and the release kinetics of furosemide from SR-adhesive microspheres was also studied. SR-adhesive and SR-non-adhesive microspheres showed very similar characteristics of drug release. The rotation speed did not affect the release kinetics, but higher pH increased the drug release from both microspheres. The absorption of furosemide after SR-adhesive microspheres administration to rats and dogs was significantly higher than that after SR-non-adhesive microspheres administration, which was very similar to the results obtained in humans. On the other hand, in monkeys, SR-adhesive microspheres were not able to improve the absorption of furosemide at all. These findings indicated that rats and dogs were in vivo animal models suitable for predicting the potency of SR-adhesive microspheres in humans.

Original languageEnglish
Pages (from-to)46-53
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume331
Issue number1
DOIs
Publication statusPublished - Feb 22 2007

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Microspheres
Adhesives
Animal Models
Furosemide
Dogs
Haplorhini
Gastric Mucosa
Small Intestine
Oral Administration

Keywords

  • Absorption
  • Adhesion
  • Animal model
  • Microspheres
  • Oral administration
  • Sustained-release

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Animal models for predicting potency of oral sustained-release adhesive microspheres in humans. / Nagahara, Naoki; Akiyama, Yohko; Higaki, Kazutaka; Kimura, Toshikiro.

In: International Journal of Pharmaceutics, Vol. 331, No. 1, 22.02.2007, p. 46-53.

Research output: Contribution to journalArticle

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