Impact of particle engineering on the processability and aerosolization performance of DPI formulations

S Zellnitz, E Faulhammer, T Wutscher, J G Khinast, A Paudel

Active pharmaceutical ingredient (API) particles administered via dry powder inhalers (DPIs) must exhibit an aerodynamic diameter of 1μm – 5μm. Particles of such a small size are rather cohesive and show poor flow properties. This is challenging for the dose uniformity, as a good flowing powder is required to guarantee uniform doses for example during capsule filling or dose metering within a reservoir inhaler. To overcome this problem, carrier based formulations where the small API particles are attached to larger carrier particles with adequate flowability have been invented. A crucial step during inhalation is the detachment of the API from the carrier. Only detached API particles are able to reach the lung. The detachment process is governed by API as well as carrier properties. Therefore, within this study the effect of particle engineering on capsule filling performance represented by capsule fill weight and weight variability and on aerosolization performance represented by the fine particle fraction (FPF) and the emitted dose (ED) were investigated. Inhalation grade lactose was used as carrier material as received and after wet surface processing. Spray dried and jet milled salbutamol sulphate served as model API. Results showed that compared to API engineering carrier engineering had a positive effect on weight variability. Moreover, the use of spray dried API particles overall decreased the FPF. Engineered carrier particles showed improved FPF but only in combination with jet milled API. The highest FPF (≈33%) was obtained for jet milled API in combination with engineered lactose carrier particles.

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