Spray-freeze-drying production of thermally sensitive polymeric nanoparticle aggregates for inhaled drug delivery: effect of freeze-drying adjuvants.

Inhalable dry-powder aggregates of drug-loaded thermally sensitive poly(caprolactone) (PCL) nanoparticles are produced using spray-freeze-drying (SFD) as the low melting point of PCL prohibits the use of high-temperature spray-drying. The effects of freeze-drying adjuvant formulation on the particle morphology, aerodynamic diameter, aqueous re-dispersibility, flowability, and production yield are examined using mannitol and poly(vinyl alcohol) (PVA) as the adjuvants. The primary role of the adjuvant is to prevent irreversible nanoparticle coalescences during freeze-drying, thereby the nanoparticle aggregates can readily re-disperse into primary nanoparticles in an aqueous environment hence retaining their therapeutic functions.