Abstract

Chitosan gel beads containing indomethacin, an acidic drug, were prepared by a polyelectrolyte complexation of sodium tripolyphosphate and chitosan. The effects of the molecular weights of chitosan hydrolysates on the release and absorption rates of indomethacin from gel beads were examined. The release rates of indomethacin decreased with increasing of molecular weight and indomethacin content. A negative correlation was observed between the molecular weight and release rate constant ( r = −0.983). The release of indomethacin depended upon the dispersion of the indomethacin solid particles in the beads, as well as the porosity, tortuosity and surface area of the matrix. The plasma concentrations ofindomethacin after oral administration of chitosan gel beads to beagle dogs exhibited the sustained-release pattern. With increasing molecular weight of chitosan, the AUC and C max were decreased, while MAT was increased. A good correlation was observed between the molecular weight of chitosan or dissolution rate constant and the MAT or AUC. The results revealed that the chitosan gel beads composed of chitosan hydrolysate, of molecular weight 25 000, might be the best for the sustained-release preparation of indomethacin. It was suggested that the absorption of other drugs could be controlled by the proper selection of chitosan hydrolysate of optimal molecular weight and predicted from in vitro dissolution tests.

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