Transferosomes are ultra-flexible vesicular carriers capable of deforming and penetrating the stratum corneum, enhancing dermal and transdermal delivery. Transferosomes were developed and optimized using Design-Expert software (version 13). To overcome ondansetron HCls poor solubility, low oral bioavailability, and first-pass metabolism, transferosome-based transdermal patches were developed. Transferosomes containing soya lecithin and edge activators (Tween 80 or Span 80) were prepared by the thin-film hydration technique and evaluated for vesicle size, zeta potential, entrapment efficiency, and drug release. The optimized tween 80-based formulation (F-opt) showed spherical vesicles of 131 nm, 93% entrapment efficiency, and sustained 98.06 ± 0.53% drug release over 12 h, following zero-order, non-Fickian kinetics. FT-IR confirmed drug–excipient compatibility. The optimized transferosomal patch (T-opt) exhibited better permeability (7.06 ± 0.99) than the conventional patch (5.91 ± 0.65), while stability studies showed no significant changes after one month. Tween 80-based ondansetron HCl transferosomes demonstrated excellent stability, high entrapment, and enhanced transdermal permeability, making them a promising system for sustained antiemetic therapy.

Keywords: Transferosomes; Ondansetron Hydrochloride; Transdermal Delivery; Permeation;