Objective: The aim of this study is to develop, characterize and evaluate (in vitro and in vivo) a novel colon-targeted bioadhesive microsphere (BAM) containing metronidazole (MTZ).
Methods: BAMs are prepared using Assam Bora rice starch as a natural bioadhesive polymer by a double emulsion solvent evaporation method.
Results: The prepared microspheres showed a uniform spherical shape, with excellent retention time. The in vitro drug release study of the optimized formulations, in different physiological environments, confirmed the insignificant release of metronidazole in the physiological conditions of the stomach (10 - 12.5%) and small intestine (< 25%). Further, fast and major drug release in cecal content (> 90) indicated that the release of the drug was unaffected by the hostile environment of the gastrointestinal tract (GIT). In vitro bacterial inhibition studies illustrated that MTZ loaded BAMs, inhibiting metronidazole-sensitive Bacteroides fragilis and selected BAMs (F1 - F7), have an equivalent or higher zone of inhibition than the marketed formulation. An in vivo organ distribution study of MTZ revealed that Assam Bora rice starch-based microspheres were relatively intact in the upper part of GIT, and the drug was released only after reaching the colon, owing to the microbial degradation of Assam Bora rice starch by microflora residing in the colon.
Conclusion: MTZ release patterns exhibited slow and extended release over longer periods of time, which shows the potential of Assam Bora rice starch microspheres as a drug carrier for an effective colon-targeted delivery system.