Spray dried mannitol carrier particles with tailored surface properties – The influence of carrier surface roughness and shape

Abstract

The aim of this work was to study the performance of mannitol carrier particles of tailored surface roughness in dry powder inhaler formulations. Carrier particles of different surface roughness were prepared by spray drying of aqueous mannitol solutions at different outlet temperatures at a pilot-scale spray dryer. However, the carrier particles did not only change in surface roughness but also in shape. This is why the impact of carrier shape on the performance of carrier based dry powder inhalates was evaluated also. The highest fine particle fraction (FPF), that is the amount of active pharmaceutical substance, delivered to the deep lung, is achieved when using rough, spherical carrier particles (FPF=29.23±4.73%, mean arithmetic average surface roughness (mean Ra)=140.33±27.75nm, aspect ratio=0.925). A decrease of surface roughness (mean Ra=88.73±22.25nm) leads to lower FPFs (FPF=14.62±1.18%, aspect ratio=0.918). The FPF further decreases when irregular shaped particles are used. For those particles, the micronized active accumulates within the cavities of the carrier surface during the preparation of the powder mixtures. Upon inhalation, the cavities may protect the active from being detached from the carrier.