In vivo evaluation of a sustained-release multiple-unit floating system containing nitrendipine

Purpose: A multiple-unit floating drug delivery system was developed to prolong the gastric residence time (GRT) and increase the oral bioavailability of the drug. Methods: An emulsion solvent diffusion method was used to prepare the microballoons (MB) using nitrendipine as a model drug. Nonfloating microspheres (NFM) were also prepared using the same polymer. Gamma scintigraphy of both the 99mTc-labeled MB and NFM was carried out in volunteers to compare the gastric residence times. In addition, MB was orally administered to albino rabbits to determine the pharmacokinetic parameters, which were compared with that of conventional tablets. Results: The optimized formulations of MB were found to have favorable in-vitro-floating characteristics. The GRT was over 5 h for the MB of nitrendipine, which was longer than that of the NFM (1.5 h). The relative oral bioavailability of nitrendipine-loaded MB was found to be increased about 1.66-fold in comparison with that of the commercial tablet. Conclusion: Microballoons which exhibit both excellent buoyancy and a suitable release rate can be prepared by the emulsion solvent diffusion method. The results suggest that the multiple-unit floating drug delivery system can prolong the GRT and significantly improve the bioavailability.

Keywords: Microballoons Multiple unit floating system Gastric residence time Gamma scintigraphy Bioavailability