Design of Experiment (DoE) Based Optimization of Ornidazole-Loaded Alginate Beads for pH-Sensitive Controlled Drug Release

Objective: The aim of this study was to develop and optimize ornidazole (ORN)-loaded sodium alginate beads using a Design of Experiments (DoE) approach and to investigate the effects of formulation variables on bead properties and pH-sensitive controlled drug release behavior.Methods: A full 2³ factorial design was employed to evaluate the effects of sodium alginate concentration, CaCl₂ concentration and drug amount on the properties of alginate beads prepared by the ionotropic gelation technique. The prepared formulations were characterized in terms of morphology, bead size (BS), encapsulation efficiency (EE), swelling index and in vitro drug release behavior. Drug release kinetics were analyzed using different mathematical kinetic models. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) analyses were also performed.Results: Increasing alginate concentration resulted in the formation of spherical, homogeneous and mechanically stable beads, while lower concentrations produced disordered and clustered structures. Higher alginate and CaCl₂ concentrations increased encapsulation efficiency due to the formation of a stronger cross-linked polymer network. Swelling studies exhibited marked pH-sensitive behavior with limited swelling in acidic environments and significantly increased swelling at pH 6.8. In vitro release studies revealed a pH-dependent controlled release profile characterized by limited drug release under gastric conditions and increased release in the intestinal environment due to polymer relaxation and matrix erosion.Conclusion: The developed alginate beads exhibited pH-sensitive swelling and controlled drug release characteristics, demonstrating their potential as a promising oral controlled-release delivery system for ORN. The study presents a systematically optimized and comprehensively characterized ORN-loaded alginate bead formulation with pH-responsive controlled release properties, highlighting the applicability of the DoE approach in the development of reproducible alginate-based oral drug delivery systems.