A review on the superiority of spray freeze drying over spray drying method in the preparation of nano composite microcarriers (NCMs) for pulmonary drug delivery

Abstract

It is difficult to formulate nanoparticles for deep lung delivery and several techniques struggle in terms of nanoparticle stability. Spray freeze drying (SFD) is proposed here for the manufacture of inhalable nano composite microcarriers (NCM). Including polymeric and lipid nanoparticles, various nanostructures have been prepared and defined. Nanoparticle suspensions were co-sprayed into a cooled, stainless steel spray tower with an appropriate cryoprotectant, followed by freeze-drying to form a dry powder while spray dried (SD) compositions were equivalent as controls. SFD-NCM has greater specific surface areas (67-77 m2/g) and lower densities (0.02 g/cm3) than their respective SD-NCM areas. SFD provided NCM with a mass median aerodynamic diameter (MMAD) of 3.0 ± 0.5 lm and fine particle fraction (FPF 6 5.2 lm) of 45 ± 1.6 % with aerodynamic efficiency comparable to SD-NCM, except for NCM for lipid-based nanocarriers. However, in terms of preserving the particle size of all the polymeric and lipid nanocarriers investigated after reconstitution, SFD was superior to SD (Sf/Si ratio for SFD 1 versus >1.5 for SD). The cooled air SFD has proven to be an effective technique to prepare NCM for pulmonary delivery while preserving the nanoparticles' stability.