IN-VIVO EVALUATION OF SUSTAINED-RELEASE MICROSPHERES OF METOCLOPRAMIDE HYDROCHLORIDE IN BEAGLE DOGS

The in vivo absorption characteristics of metoclopramide hydrochloride microspheres prepared from cellulose propionate polymer by an emulsion-solvent evaporation method were evaluated using six male beagle dogs. Metoclopramide was administered intravenously at a dose of 4 mg and orally as a single dose (10 mg) of microspheres and conventional tablets (Plasil(R)) on three separate occasions. Statistically significant differences were found between the two oral treatments in both the time and magnitude of the peak generated (p < 0.05). The absorption rate (C-max/AUC) was significantly slower following the administration of microspheres. No significant difference was found between the two treatments in the area under the plasma concentration-time curve (AUG), indicating a comparable extent of absorption. The mean residence time (MRT) and mean absorption time (MAT) were dramatically increased following microsphere administration compared to the conventional tablets. The absolute bioavailability of metoclopramide from the microspheres and the conventional tablets was 72 and 65%, respectively. The in vivo results were found to be consistent with the in vitro availability of the drug.