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

Handling low-density pharmaceutical products, such as lyophilises, 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).

Highlights

• SFD increases the processability of thermolabile drugs.

• SFD produces highly porous, low-density microspheres.

• The flowability of lyospheres® is typically superior to mass-equivalent spray-dried particles.

• High sphericity of lyospheres® can compensate for low density regarding flowability.

• Mechanical stability of lyospheres® is observed with solid contents ≥5%.

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 with 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.

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Following excipients were also used in the research for comparison: Cellets®200, FlowLac®100, Pearlitol®200 SD

Annika Rautenberg, Alf Lamprecht, Spray-freeze-dried lyospheres: Solid content and the impact on flowability and mechanical stability, Powder Technology, 2022, 117905, ISSN 0032-5910, https://doi.org/10.1016/j.powtec.2022.117905