Abstract 

Glibenclamide, a BCS class II antidiabetic drug, exhibits dissolution-limited absorption due to its poor solubility. A Self-Nanoemulsifying Drug Delivery System (SNEDDS) offers a promising strategy to enhance its oral bioavailability by improving drug solubilization and formulation stability. This study aimed to optimize the proportions of Tween 80 and propylene glycol in glibenclamide SNEDDS using a simplex lattice design, with transmittance and emulsification time as the main responses. Eight formulations were evaluated, and the optimum composition was determined using the Desirability Index. Tween 80 exerted a greater positive effect on transmittance, while propylene glycol more effectively reduced emulsification time. The optimized SNEDDS exhibited desirable characteristics, including a clear light-yellow appearance, pH 6.59 ± 0.021, particle size 115.8 nm, monodisperse distribution (PDI 0.459), and zeta potential –17.5 mV. Stability testing showed no phase separation. Overall, the optimized SNEDDS provided improved emulsification behavior and stable physicochemical properties, supporting its potential to enhance the oral delivery of glibenclamide.