Jet-vortex spray freeze drying for the production of inhalable lyophilisate powders

Spray-freeze-dried powders were suggested for nasal, epidermal (needle-free injection) or pulmonary application of proteins, peptides or nucleic acids. In spray-freeze-drying processes an aqueous solution is atomized into a refrigerant medium and subsequently dried by sublimation. Droplet-stream generators produce a fast stream of monodisperse droplets, where droplets are subject to collisions and therefore the initial monodispersity is lost and droplets increase in diameter, which reduces their suitability for pulmonary application. In jet-vortex-freezing, a droplet-stream is injected into a vortex of cold process gas to prevent droplet collisions. Both the injection position of the droplet-stream and the velocity of the cold gas vortex have an impact on the size distributions of the resulting powders. A model solution containing mannitol (1.5% m/V) and maltodextrin (1.5% m/V) was sprayed at 5 droplet-stream positions at distances between 1 mm and 30 mm from the gas jet nozzle and 5 gas velocities (0.8-6.8 m/s) at a process temperature of -100 degrees C. Mean geometric diameters of the highly porous particles (bulk density: 0.012 +/- 0.007 g/cm(3)) ranged between 55 +/- 4 and 98 +/- 4 mu m. Evaluation of the aerodynamic properties by Next-Generation-Impactor (NGI) analysis showed that all powders had high emitted doses (98 +/- 1%) and fine-particle fractions ranged between 4 +/- 1% and 21 +/- 2%. It was shown that jet-vortex freezing is a suitable method for the reproducible production of lyophilized powders with excellent dispersibility in air, which has a high potential for nasal and pulmonary drug delivery. (C) 2016 Elsevier B.V. All rights reserved.