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 emulsio n-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 table ts (Plasil(R)) on three separate occasions. Statistically significant differences were found between the two oral treatments in both the tim e and magnitude of the peak generated (p < 0.05). The absorption rate (C-max/AUC) was significantly slower following the administration of m icrospheres. No significant difference was found between the two treat ments in the area under the plasma concentration-time curve (AUG), ind icating a comparable extent of absorption. The mean residence time (MR T) and mean absorption time (MAT) were dramatically increased followin g 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 res ults were found to be consistent with the in vitro availability of the drug.