Nasal powders drug delivery strategies for upper airways viral infections treatment

This study reports the successful development of microparticulate and powder formulations of the antiviral drugs favipiravir and chloroquine diphosphate, designed for nasal and lower airway delivery using the TurbospinⓇ breath-actuated device. Favipiravir was co-formulated with methyl-β-cyclodextrin via spray-drying to enhance dissolution and permeation rates, aiming to repurpose the drug for early SARS-CoV-2 prophylaxis and treatment through a potential synergistic antiviral effect. Similarly, chloroquine diphosphate microparticles produced by spray-drying exhibited an amorphous drug state, suitable aerodynamic particle size distribution, and efficient aerosol deposition throughout the upper airways in in vitro nasal models under both basal and sharp sniff airflow conditions. Furthermore, favipiravir nanocrystals have been produced by wet ball milling with TPGS, characterized by a stable crystalline form, improved dissolution kinetics, and enhanced permeation across rabbit nasal mucosa, demonstrating a clear correlation between particle size reduction and increased bioavailability. Although further optimization is required, these findings highlight the promise of nasal inhalation of spray-dried microparticulate and nanocrystal formulations as effective delivery systems for loco-regional antiviral action.