TY - JOUR
T1 - Animal models for predicting potency of oral sustained-release adhesive microspheres in humans
AU - Nagahara, Naoki
AU - Akiyama, Yohko
AU - Higaki, Kazutaka
AU - Kimura, Toshikiro
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2007/2/22
Y1 - 2007/2/22
N2 - 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.
AB - 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.
KW - Absorption
KW - Adhesion
KW - Animal model
KW - Microspheres
KW - Oral administration
KW - Sustained-release
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U2 - 10.1016/j.ijpharm.2006.09.010
DO - 10.1016/j.ijpharm.2006.09.010
M3 - Article
C2 - 17098383
AN - SCOPUS:33846587976
VL - 331
SP - 46
EP - 53
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1
ER -