Influence of specific gravity and food on movement of granules in the gastrointestinal tract of rats.
The suitability of rats as an animal model for estimating the bioavailability of controlled-release granules in humans was investigated. Non-disintegrating granules (diameter of 0.8 mm; specific gravity of 0.9-1.85) were used as a model preparation. Twenty granules were administered to fed rats, fasted rats and rats given soft food, and the number of granules remaining in the gastrointestinal tract was counted at suitable intervals. Granules with a specific gravity of 1.25 administered to fasted rats were rapidly emptied from the stomach with a 50% gastric emptying time of 1 h as compared with granules with a specific gravity of less than 1.0 or with a high specific gravity such as 1.85. The presence of food in the stomach reduced the emptying rate of granules. The mean transit time of granules through the small intestinal tract was not influenced by the specific gravity or the presence of food. The mean transit time was about 3 h. It was found that the transit profile of granules through the gastrointestinal tract in rats was similar to that of granules in humans. Accordingly, it is possible to use rats at the preformulation stage for estimating the bioavailability of controlled-release granules in humans.
Mori
M
M
Shirai
Y
Y
Uezono
Y
Y
Takahashi
T
T
Nakamura
Y
Y
Makita
H
H
Nakanishi
Y
Y
Imasato
Y
Y
D000818:Animals; D005502:Food; D005772:Gastrointestinal Transit / Q000187:drug effects*; D008297:Male; D008863:Microspheres; D051381:Rats; D011919:Rats, Inbred Strains; D013046:Specific Gravity