Typical dry powder inhalation (DPI) formulations are composed of an Active Pharmaceutical Ingredient (API) and a carrier excipient, most usually lactose. It is also common to add a second grade of lactose, known as fine lactose, in order to improve the fine particle fraction (FPF) of the formulation. However, increasing the percentage of fine excipient can also have a negative effect on the rheology of the formulation, leading to loss of efficiency on the downstream process, like high rejection rates during automatic capsule filling steps. Additionally, an impact on the overall flowability may also lead to aerosolization challenges upon device actuation, with a potential negative impact on the Emitted Mass (EM). For these reasons the rheological characterization of these powders becomes important.
In this work, different grades of coarse and fine lactose were used to prepare excipient blends with different percentages of fine lactose. Rheology testing was conducted using an FT4 powder rheometer. A partial least squares (PLS) regression was applied to the gathered data and a high degree of correlation was found between formulation composition and rheology parameters. It was observed that the basic flowability energy (BFE), the conditioned bulk density (CBD) and the pressure drop (PD) across the powder bed are mainly governed by the percentage of fines and the particle size of the coarse lactose. On the other hand, the aeration energy (AE) depends mostly on the percentage of fines and the particle size of the fine lactose. This model allows the prediction of rheology parameters of DPI formulation blends which are then correlated with capsule filling and device performance in Part B of this article.