Letrozole-loaded nonionic surfactant vesicles prepared via a slurry-based proniosome technology: Formulation development and characterization

Abstract

Slurry-based Letrozole (LTZ)-loaded proniosomes were designed using sucrose or sorbitol as carriers and various ratios of cholesterol (CH) and Tween 80 (T80) as lipid composition. Proniosomes were hydrated and probe-sonicated to generate nano-vesicles. The proniosome powders were characterized in terms of morphology using scanning electron microscopy, and drug crystallinity using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The niosomes generated from proniosomes were characterized and compared to conventional niosomes, in terms of size, zeta potential, drug entrapment, storage stability, and drug release. All formulations had size measurements in the range of 100–194 nm, polydispersity index (PDI) values below 0.3, and zeta potential values below – 23 mV. Drug entrapment was the highest for niosomes generated from sucrose-based proniosomes (CH:T80; 1:1), reaching 74% compared to less than 50% for conventional niosomes. Storage for 3 months at 4 °C resulted in minor drug leakage whilst most drug was leaked from vesicles stored at room temperature. DSC and XRD studies showed that LTZ was converted into its amorphous form upon incorporation into proniosomes. Drug release exhibited a biphasic pattern, being fast at the first 24 h (up to 65% released) followed by a very slow release phase for a duration of one month, releasing at least 95%. The release profile of niosomes fits best with the Higuchi model. Overall, in this study, a facile approach to generating niosomes incorporating LTZ using a slurry-based proniosome technology was demonstrated. The niosomes provided high drug entrapment and controlled biphasic release over one month.