Influence of particle shape of spray-dried mannitol carriers on powder flow and aerodynamic properties

Mathias Mönckedieck, Jens Kamplade, Phanuel Fakner, Hartwig Steckel, Peter Walzel

The application of coarse sugars (> 50 µm) in combination with adhesive active pharmaceutical ingredients (> 5µm) in dry powder inhalers is a widely used system to overcome the dosing problems due to the cohesiveness of the small active. A good flowability of the drug carrier is the essential requirement for comparting the powder dose accurately. The drug is then detached from the carrier by the shear forces during inhalation. In this study, mannitol carrier particles were prepared by spray drying using different parameters to gain particles of different particle sizes and surface morphologies, which were identified as properties with an influence on the flowability. It could be shown in a design of experiments study, that it is possible to generate particles with various flowabilities in dependence on the rotary speed and the axial air stream temperature of the spray tower. High temperatures led to indented particles with a lower flowability, while low temperatures generate spherical particles with good flow properties. The particle size, altered by different rotary speeds, has no significant influence for spherical carrier particles but for indented particles, where smaller particles own a better flowability than larger ones. In further experiments, the inhaler performance was tested with a commercial inhaler device (Novolizer®) by using the next generation impactor and the fine particle fraction was compared to the appropriate flowabilities. Results exhibit that the fine particle fraction is strongly depending on the flowability of the carrier particles. For less flowable powders, a lower the fine particle fraction was found in impaction experiments.

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