β-Cyclodextrin/Chitosan Microparticles for Sustained Release of Dapagliflozin

Introduction: Dapagliflozin, a selective Sodium-Glucose Co-Transporter 2 (SGLT2) inhibitor, is widely used in the treatment of diabetes by promoting glucose excretion through urine. However, its poor aqueous solubility and rapid elimination limit its therapeutic efficacy, highlighting the need for an improved drug delivery system. This study aimed to formulate and evaluate β- cyclodextrin (β-CD)-based microparticles containing dapagliflozin to provide its sustained release. Methods: Microparticles were prepared in a 1:3 molar ratio of drug to β-CD using the ionic gelation method, with chitosan used as a coating polymer at varying concentrations. The microparticles were characterized for percentage yield, drug content, flow properties, swelling index, particle size (using optical microscopy), surface morphology (using scanning electron microscopy), and in vitro drug release. Results: The particle size of the microparticles ranged from 912.8 μm to 1019.2 μm. β-CD-containing microparticles (D1 and D3) exhibited higher drug content and swelling indices compared to non-β-CD microparticles (D2 and D4). In vitro release studies showed that β-CD microparticles exhibited a slower, sustained drug-release profile. Kinetic modeling revealed that microparticle formulation D1 followed the Korsmeyer-Peppas model, indicating a combination of diffusion and polymer relaxation as the release mechanism, while D2 and D3 followed zero-order kinetics, and D4 followed first-order kinetics. Discussion: The study showed that β-cyclodextrin (β-CD)-containing microparticles (D1 and D3) had higher yields, better swelling indices, and larger particle sizes due to enhanced cross-linking, hydrophilicity, and stronger polymeric interactions compared to non-β-CD formulations (D2 and D4). The presence of β-CD improved drug encapsulation efficiency and hydration, supporting sustained drug release, while higher chitosan concentration led to more compact matrices with controlled swelling. SEM analysis confirmed that β-CD formulations had smoother and denser surfaces, whereas non-β-CD microparticles were rougher and more porous. Drug release studies showed that β-CD significantly slowed the diffusion of dapagliflozin by forming stable inclusion complexes, resulting in sustained release. In contrast, non-β-CD formulations released the drug more rapidly due to their greater porosity. Drug release kinetics indicated non-Fickian, zero-order, and first-order release patterns across formulations, confirming the potential of β-CD-based microparticles for controlled drug delivery applications. Conclusion: The study demonstrated that β-CD/dapagliflozin microparticles coated with 1% (w/v) chitosan solution provided a sustained drug release profile. The sustained release potential of β-CD microparticles makes it an appropriate approach for the controlled delivery of dapagliflozin.