Emulsion-Gelation Strategy for Developing Buoyant Multiparticulate Systems of Metronidazole with Prolonged Gastric Residence

Abstract

The present study aimed to develop and optimize a buoyant multiparticulate drug delivery system of Metronidazole using the emulsion–gelation technique to overcome the limitations of conventional oral formulations such as short half-life, variable absorption, and frequent dosing. Preformulation studies confirmed the compatibility of Metronidazole with excipients through FTIR and DSC analysis, while solubility evaluation demonstrated higher dissolution in acidic medium, justifying a gastro-retentive approach. Beads were prepared using ionotropic and emulsion–gelation methods, and the effects of sodium alginate concentration, calcium chloride level, and liquid paraffin content were systematically investigated. Optimized beads (3% alginate, 1% CaCl₂, 20% oil) exhibited uniform spherical morphology, mean particle size of 2.3 ± 0.1 mm, and high entrapment efficiency (90.2 ± 1.8%). The buoyancy studies revealed a floating lag time of less than one minute with sustained floating for more than 12 hours. In vitro dissolution demonstrated controlled release, with ~70% release at 8 hours and ~91.5% at 12 hours. Kinetic analysis indicated that the drug release followed the Higuchi model (R² = 0.989) with non-Fickian diffusion, suggesting a combination of diffusion and matrix erosion mechanisms. The study concludes that the emulsion–gelation approach provides a robust platform for developing gastro-retentive multiparticulate systems of Metronidazole, ensuring prolonged gastric residence, sustained release, and potential improvement in therapeutic efficacy and patient compliance...