BIOAVAILABILITY OF MECLOFENAMATE FROM EXPERIMENTAL SUSTAINED-RELEASE MICROCAPSULES IN BEAGLE DOGS

This investigation was carried out to evaluate the absorption characte ristics of experimental meclofenamate sustained-release microcapsules, prepared by an emulsion-solvent evaporation method using high molecul ar weight cellulose propionate polymer and polyethylene glycol (PEG) 2 000 in a ratio of 1:2:1 drug:polymer:PEG, using eight male beagle dogs . Meclofenamate was administered intravenously at a dose of 40 mg and orally as a single dose (50 mg) of conventional capsules (Meclomen(R)) , oral solution and microcapsules on four separate occasions. Statisti cally significant differences were observed between the microcapsules and the other two oral treatments in both the peak plasma concentratio n (C-max) and the time of peak concentration (T-max). No significant d ifference was found between the three oral treatments in the area unde r the plasma concentration-time curve (AUG), indicating a comparable e xtent of absorption. The absorption rate (C-max/AUC) was significantly slower following the administration of microcapsules. Both the mean r esidence time (MRT) and the mean absorption time (MAT) were dramatical ly increased following oral administration of the microcapsules compar ed to the conventional capsules and the oral solution. The mean (in-vi vo) dissolution time (MDT) for the prepared microcapsules was 2.14 h a nd for the conventional capsules 0.3 h, which were found to be consist ent with the in-vitro availability of the drug. Duncan's multiple rang e test indicated no significant difference between the oral solution a nd the conventional capsules in any of the calculated pharmacokinetic parameters. The absolute bioavailability from the oral solution, the c onventional capsules and the experimental microcapsules was 74.6, 67.9 and 72.5%, respectively.