This study aims to investigate the effect of carrier characteristics and dosator capsule filling operation on the in vitro deposition of mixtures containing salbutamol sulphate (SS) and lactose and mannitol as model carrier materials. The carrier surfaces of lactose and mannitol were modified via wet decantation. The impact of the decantation process on the properties of carriers was investigated by laser diffraction, density and powder flow measurements, N2 physisorption, small and wide angle X-ray scattering (SWAXS) and scanning electron microscopy (SEM). Differences in carrier type and untreated and decanted materials were identified and the SAXS measurements proved to be a promising technology confirming the successful removal of fines. Adhesive carrier API mixtures with carrier-to-API ratio of 99:1 wt% were prepared, mixture homogeneity was tested and subsequently the mixtures were filled into capsules at different process settings. Finally, the influence of the decantation process on the in vitro performance of the adhesive mixtures was tested with a next generation impactor. For lactose, the decantation decreased the fine particle fraction (FPF) of SS, whereas the FPF of mannitol as a carrier was only affected by the capsule filling process. In summary, the DPI formulation based on untreated lactose, especially by capsule filling using a dosing chamber to powder layer (compression) ratio of 1:2, proved to be superior in terms of the dosing accuracy (RSD < 0.8%) and the in vitro aerodynamic performance (FPF of 12%).
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