Bioavailability of meclofenamate from experimental sustained-release microcapsules in beagle dogs

Abstract

Abstract This investigation was carried out to evaluate the absorption characteristics of experimental meclofenamate sustained-release microcapsules, prepared by an emulsion-solvent evaporation method using high molecular weight cellulose propionate polymer and polyethylene glycol (PEG) 2000 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®), oral solution and microcapsules on four separate occasions. Statistically significant differences were observed between the microcapsules and the other two oral treatments in both the peak plasma concentration ( C max ) and the time of peak concentration ( T max ). No significant difference was found between the three oral treatments in the area under the plasma concentration-time curve (AUC), indicating a comparable extent of absorption. The absorption rate ( C max /AUC) was significantly slower following the administration of microcapsules. Both the mean residence time (MRT) and the mean absorption time (MAT) were dramatically increased following oral administration of the microcapsules compared to the conventional capsules and the oral solution. The mean (in-vivo) dissolution time (MDT) for the prepared microcapsules was 2.14 h and for the conventional capsules 0.3 h, which were found to be consistent with the in-vitro availability of the drug. Duncan's multiple range test indicated no significant difference between the oral solution and the conventional capsules in any of the calculated pharmacokinetic parameters. The absolute bioavailability from the oral solution, the conventional capsules and the experimental microcapsules was 74.6, 67.9 and 72.5%, respectively.