Spray freeze dried niclosamide nanocrystals embedded dry powder for high dose pulmonary delivery
Shengyu Zhang, Shen Yan, Kangwei Lu, Shixuan Qiu, Xiao Dong Chen, Winston Duo Wu
Based on the drug repositioning strategy, niclosamide (NCL) has shown potential applications for treating COVID-19. However, the development of new formulations for effective NCL delivery is still challenging. Herein, NCL-embedded dry powder for inhalation (NeDPI) was fabricated by a novel spray freeze drying technology. The addition of Tween-80 together with 1,2-Distearoyl-sn-glycero-3-phosphocholine showed the synergistic effects on improving both the dispersibility of primary NCL nanocrystals suspended in the feed liquid and the spherical structure integrity of the spray freeze dried (SFD) microparticle. The SFD microparticle size, morphology, crystal properties, flowability and aerosol performance were systematically investigated by regulating the feed liquid composition and freezing temperature. The addition of leucine as the aerosol enhancer promoted the microparticle sphericity with greatly improved flowability. The optimal sample (SF– 80D-N20L2D2T1) showed the highest fine particle fraction of ∼47.83%, equivalently over 3.8 mg NCL that could reach the deep lung when inhaling 10 mg dry powders.
Fine particle fraction, NCL-embedded dry powder for inhalation (NeDPI), Particle formation mechanism, Spray freeze drying, Structure-performance relationship