Carrier microstructure and performance of dry powder inhalation mixtures: A step towards universal performance prediction model

Ahmed O. Shalash, Nawal M. Khalafallah, Abdulla M. Molokhia, Mustafa M.A. Elsayed

Performance-explaining theories are often limited. In carrier-based dry powder inhalers (DPIs), this is mainly underlain by the large number of interacting variables (device, drug and carrier).

In this study, the relationships between carrier particle size and permeability, and between microstructural properties and inhalation performance are explored using eleven different carrier grades. Hydroxypropyl-β-cyclodextrin, lactose anhydrous, lactose monohydrate, dextrose anhydrous, dextrose monohydrate, xylitol and sucrose were used as carriers to prepare fifteen 1% w/w fluticasone propionate inhalation mixtures. The carriers were characterized for particle size using laser diffraction and for pore-size distribution and air permeability using mercury intrusion porosimetry. The in-vitro performances after aerosolization from an Aerolizer ® at 60 L.min-1 were assessed using Next Generation Impactor ®.

The carriers differed in their particle size, fine contents, particle shapes, and air permeabilities. CD had a remarkable nanoporosity. The performances of the inhalation mixtures varied widely. Optimum dispersion was achieved at carrier permeability of 3.0 Darcy. Lower FPFs were found above and below this value.

However, to predict the performance of the deviating nanorough carriers in a single model, the carrier roughness scales should be taken into account. Taking porosity scales into account in a simple multivariate model, resulted in a performance predictive relationship with an adjusted R2=0.98.

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