Exploring the influence of drug content on DPI powder properties and potential prediction of pulmonary drug deposition

Based on dry powder inhaler (DPI) inhalation process, powder properties have a key influence on fluidization and deagglomeration behavior during aerosol generation. The aim of this study was to explore the influence of drug content on DPI powder properties and further reveal the correlations between powder properties and pulmonary deposition efficiency. Using salbutamol sulfate as a model drug, Lactohale® 100 as carrier, carrier-based binary mixtures were prepared at drug content from 0.5 to 10% (w/w), characterized with powder rheometer, faraday cage and Next Generation Impactor. It was demonstrated that drug content had a remarkable influence on powder behavior, and good correlations between powder properties and fine particle fraction (FPF) were established in drug content range 0.5-7%. A negative correlation between basic flowability energy and FPF, reflected a good flowability is beneficial for powder fluidization. Further properties characterization, including aeration ratio, permeability, pre-shear stress and aerodynamic specific charge, suggested a strong interaction is beneficial for powder deagglomeration. It's the first time that interaction indicator and flowability indicator were extracted with principal component analysis (PCA). In conclusion, drug content has a significant influence on powder properties. DPI formulations with a stronger interaction and meanwhile a better flowability are desirable for enhanced pulmonary drug delivery.