Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation

摘要

The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8h. The optimized formulation (F10) exhibited prolonged drug release (more than 8h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n=0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet.