Influence of fines on commercial lactose carriers and their dry powder inhalation performance

Mats Hertel, Eugen Schwarz, Eva Maria Littringer, Mirjam Dogru, Regina Scherlie├č, Hartwig Steckel

Many efforts have been made in the past to explain the beneficial effect of fines but the exact mechanisms how these fine lactose particles alter the performance of dry powder inhaler (DPI) formulations has remained unclear. In this study the influence of fines added to commercially available lactose carriers is investigated. For this purpose, two different-sized carriers were blended with different concentrations of fines and the model drug budesonide in different blending orders. All blends were prepared with a high shear mixer, which would make an upscaling possible, at different rotational speeds and mixing times. Afterwards the blends were tested with an inhaler device (Novolizer®) by using the Next Generation Pharmaceutical Impactor (NGI). The fine particle fraction (FPF), the fine particle dose (FPD) and the mass median aerodynamic diameter (MMAD) were then compared with the factors rotation speed, blending time, blending order and the amount of fines. It could be shown that all factors have an impact on the FPF and FPD. As an explanation all common postulated theories come into consideration. With the help of blending order results and SEM pictures the saturation of active sites, the function of the fines as a buffer during blending and the formation of drug-fines agglomerate could be proven. Overall, the great benefit of fines for commercial lactose carrier and their DPI performance could be shown in this work as well as the importance of a better understanding of the exact mechanism of their acting, in particular for the blending process.

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