Spray-freeze-dried lyospheres: Solid content and the impact on flowability and mechanical stability

Annika Rautenberg, Alf Lamprecht

Abstract

Handling low-density pharmaceutical products, such as lyophilisates, presents a challenge. Spray-freeze-dried (SFD) particles, overcoming many of these challenges, were analysed regarding flowability, mechanical stability, product properties (morphology, particle size) and physicochemical properties of the spraying solution (density, viscosity, freezing point, glass transition). Mannitol-polyvinylpyrrolidone 25 (PVP 25) solutions in concentrations ranging from 2.5 to 20% (w/w) were spray-freeze-dried with three different nozzle-diameters (25, 50, 100 μm). Results show it is not only possible to spray SFD solutions with various physicochemical properties (viscosity ≤3.07 ± 0.04 mPa·s, freezing point depravation ≤1.867 ± 0.058 °C) to produce a free-flowable powder but also the possibility to regulate median particle size via nozzle diameter and solid content of the solution (147–458 μm). All formulations containing at least 0.1 g/ml solid content exhibit a flowability comparable to commercially available excipients products with ten times higher densities, a good or passable flowability (angle of repose ≤40°) and no significant decrease in median particle size after mechanical stability testing (p ≥ 0.05), which can both be attributed to their high average sphericity (> 0.90). This shows that SFD is a suitable method to produce freeze-dried flowable products that maintain their mechanical stability.

Keywords

Spray-freeze-drying, Lyospheres, Low-density powder