A closer look on the dispersion behaviour of Parteck^® M DPI – based interactive mixtures: improving the fine particle fraction by the addition of fines

N Rhein¹, G Birk², R Scherließ¹

¹Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany

²Merck KGaA, Frankfurter Straße 250, 64293 Darmstadt, Germany

Summary

Different methods are known to improve the fine particle fractions of dry powder inhalation formulations. One example is the addition of fines. It is a simple approach to saturate active sites, reduce press-on forces or form easy-to-disperse API (active pharmaceutical ingredients)-fines-agglomerates. But this process is often a disadvantage for the consistency in dosing delivery, because an increase of fines leads to poorer powder flow behaviour. In this study the addition of up to 70 % fines to the Parteck^® M DPI carrier was investigated with the aim to maximise fine particle fraction (FPF). Rheological measurements were performed to get a closer into the process of surface coverage with fines. The addition of fines maximised FPF for budesonide as well as for salbutamol sulphate blends. These increases of the FPF component were independent of the used inhaler devices. In this context the saturation of the indentations (active sites) was the most important effect. Also, an increase of the fluidisation energy was observed, indicating a rise in cohesion forces for the blends with a higher amount of fines. The small standard deviation associated with cascade impactor-based measurements of powder aerodynamic particle size distribution as well as with the measurements of the total metered dose are indicative that the Parteck^® M DPI has a constant dosing behaviour even with the addition of high amounts of fines.