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Background: Glibenclamide is a lipophilic drug widely used in type 2 diabetes treatment. However, its low bioavailability limits its use. Thus, novel formulations should be applied to improve the drug’s bioavailability. Objectives: This study aimed to develop alternative carriers for oral delivery of glibenclamide. For this purpose, two biocompatible polymers, poly(e-caprolactone) and poly(butylene adipate) were formulated as microparticles (MPs) capable of loading the antidiabetic drug. Methods: In this regard, as microparticle fabrication approach, the modified emulsion solvent evaporation method was applied. Physicochemical evaluation of the prepared microparticles included the examination of their morphology, degradation rate, and thermal properties. Drug entrapment, drug loading, and particle size were also investigated. Simulated intestinal medium and body fluid at 37oC were selected as dissolution media. Differential scanning calorimetry was used to investigate the crystal properties of the microparticles and drugs. Results: The developed microparticles had sizes between 0.5 and 4 μm. Poly(butylene adipate) based microparticles had a smooth surface, whereas poly(ε-caprolactone) based microparticles showed a porous surface. The DSC thermogram revealed the amorphization of the drug. Hydrolysis results exhibited a very low mass loss, while in vitro release results depicted that the dissolution rate of the prepared microparticles was higher than that of pure glibenclamide demonstrating a prolonged pattern which is ideal for minimizing the daily dose of glibenclamide. Conclusion: In this study, novel carriers for glibenclamide were successfully prepared with promising future use.