Optimization of Spanlastic Nanovesicles for Intranasal Delivery of Fexofenadine HCl: In vitro and Ex vivo Studies

Abstract

Introduction: Fexofenadine hydrochloride (FEX), a BCS Class IV antihistamine, imparts low oral bioavailability
because of its low water solubility, limited permeability, and P-glycoprotein–mediated efflux, resulting in delayed
therapeutic action in allergic rhinitis (AR). Materials and Methods: To provide controlled drug release and
improve FEX absorption, the current study set out to develop and optimize an intranasal spanlastic nanovesicular
system. Ethanol injection was used to create FEX-loaded spanlastics, which were then optimized with the help of
a Box–Behnken design and a quality-by-design methodology. Cumulative drug release and entrapment efficiency
(%EE) were systematically assessed in relation to surfactant concentration and sonication time. Results: The
optimized spanlastic formulation exhibited high EE (88.30 ± 2.20%) and sustained drug release (80.54 ± 2.16% in
8 h), closely matching predicted values. It showed nanoscale vesicle size (178.7 nm), good stability (−28.03 mV),
and uniform distribution. Zero-order release kinetics and significantly enhanced ex vivo nasal permeation compared
to FEX solution were observed. Discussion: The experimental and predicted values confirm the robustness of
the optimization model. Nanoscale size and adequate zeta potential indicate suitability for intranasal delivery.
Enhanced permeation is attributed to vesicle deformability and surfactant synergy, whereas refrigerated stability
supports formulation reliability. Conclusion: The optimized spanlastic system represents a promising and patient-
friendly intranasal delivery platform for improving the bioavailability and therapeutic performance of FEX in AR.