Formulation and Evaluation of Glibenclamide Nanocrystals for Improved Solubility and Antidiabetic Efficacy
Аннотация
The present study aimed to develop, optimize, and evaluate glibenclamide nanocrystals to enhance the dissolution rate and oral bioavailability of this BCS Class II antidiabetic drug, thereby improving its therapeutic efficacy. Glibenclamide nanocrystals were prepared using a combination method (antisolvent precipitation followed by wet bead milling). A 3² factorial design was employed to optimize formulation variables (stabilizer concentration and drug concentration) with particle size, polydispersity index (PDI), and zeta potential as response variables. Solidstate characterization confirmed partial reduction in crystallinity without chemical interaction with stabilizers. In vivo studies in diabetic rats demonstrated superior pharmacodynamic efficacy with 68.5 ± 4.2% maximum blood glucose reduction at 4 hours, compared to 42.8 ± 3.5% at 6 hours for marketed formulation. Pharmacokinetic analysis revealed 2.8-fold and 1.7-fold enhancement in oral bioavailability relative to pure drug and marketed formulation, respectively. Stability studies confirmed that lyophilized nanocrystals remained stable for 3 months under accelerated conditions. Nanocrystal technology successfully addressed the solubility and dissolution limitations of glibenclamide, resulting in significantly enhanced oral bioavailability and improved antidiabetic efficacy. This approach represents a promising strategy for optimizing the therapeutic performance of BCS Class II drugs like glibenclamide