Solubilization of Azelnidipine in TPGS Micelles: Structural Insights, Micellar Stability, and Sustained Drug Release Behavior

Abstract Polyethoxylated (PEO)-based nonionic surfactants, such as D-α-Tocopheryl polyethylene glycol succinate (TPGS), offer significant advantages in drug delivery due to their low toxicity, mild interaction with biological membranes, and ability to form stable micellar systems. This study investigates the solubilization and delivery of the poorly water-soluble drug AZP using TPGS micelles. TPGS exhibited a low critical micelle concentration (0.002% w/v), forming stable, spherical, and monodisperse micelles (9.99–13.51 nm) with high drug-loading efficiency (86%). Fluorescence quenching studies confirmed the encapsulation of AZP in the hydrophobic micellar core, protecting it from aqueous degradation. In vitro release profiles showed sustained drug release from TPGS micelles, with less than 20% drug release in 6 hours compared to 90% from free AZP. Dilution studies showed micelle stability up to 30-fold dilution, with disassembly observed at higher dilutions. These findings underscore the potential of TPGS micelles as effective nanocarriers to improve the solubility, stability, and bioavailability of hydrophobic drugs, while enabling controlled release for better therapeutic performance.