Detachment of various spray dried drugs from engineered mannitol carrier particles

Mathias Mönckedieck, Jens Kamplade, Peter Walzel, Hartwig Steckel, Nora Urbanetz & Regina Scherließ

Most dry powder inhalers (DPIs) utilise the well-established system of coarse carriers (> 50 μm) with good flow properties and fine drug particles (< 5 μm) attached to the carrier surface to overcome the cohesiveness of micronised drug particles and to ensure adequate dosing. This project was investigating the influence of carrier size and shape on the dispersion of various drug particles during inhalation. Spray drying was used to prepare mannitol carriers with different particle shapes that concurrently ranged from 50 to 80 μm in size. Six batches of different characteristics were then blended with spray dried qualities of four model drugs (salbutamol sulphate, tiotropium bromide, budesonide, formoterol fumarate) that were different in hydrophilicity to examine effects of carrier characteristics and drug properties. All interactive powder blends were aerodynamically characterised by impaction analysis using the Next Generation Impactor to correlate Fine Particle Fraction (FPF) and particle properties. Carrier shape was detected as the main factor to influence the FPF while different drugs preferred differently shaped carriers to perform best. Salbutamol sulphate was preferably detached from spherical carriers, but got entrapped in indentions, while tiotropium bromide and budesonide preferred small indentions to hide from assumed press-on forces during blending as those increase particle-particle interactions. Contrary to other drugs tested, formoterol fumarate (FOR) exhibited reduced FPFs whenever agglomerates occurred upon blending.

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