Formulation and Evaluation of Biodegradable Microsphere Hydrogel for Ocular Delivery of Metronidazole
Background: Ocular drug delivery is hindered by physiological barriers such as tear turnover and nasolacrimal drainage, leading to poor bioavailability of conventional formulations. Biodegradable hydrogel microspheres offer a promising approach for sustained ocular release of therapeutic agents. Objective: To formulate and evaluate sodium alginate Pluronic F-68 hydrogel microspheres for ocular delivery of metronidazole using a factorial design approach. Methods: Hydrogel microspheres were prepared by ionic crosslinking of sodium alginate and Pluronic F-68, with metronidazole incorporated into the polymeric matrix. Nine formulations (MH1 MH9) were developed and evaluated for entrapment efficiency, particle size, zeta potential, swelling behaviour, and in vitro drug release in simulated tear fluid. Results: Entrapment efficiency ranged from 33.62 percent to 67.37 percent, with MH7 showing the highest drug loading (33.6 percent) and encapsulation efficiency (67.37 percent). Particle size varied between 40.44 µm and 148.28 µm, with MH7 exhibiting a zeta potential of –22.1 mV, indicating good stability. Swelling studies revealed that higher sodium alginate concentrations increased water uptake, whereas higher Pluronic F-68 concentrations reduced it. In vitro release demonstrated that MH7 achieved sustained release, with 49.4 percent drug released over 24 h. Kinetic modelling indicated that drug release followed the Higuchi model (R² = 0.9925), suggesting a diffusion-controlled mechanism. Conclusion: The optimised formulation MH7 demonstrated high encapsulation efficiency, stable particle characteristics, and prolonged drug release, making it a promising candidate for sustained ocular delivery of metronidazole.