PT Unknown AU Mönckedieck, M TI Particle-particle interactions between tailored mannitol carrier particles and drug particles for inhalation PY 2016 PU Christian-Albrechts-Universität zu Kiel WP https://macau.uni-kiel.de/receive/diss_mods_00019499 LA en DE spray drying; mannitol; dry powder inhalation; design of experiments; interactive powder blends; Sprühtrocknung; Trockenpulverinhalation; Versuchsplanung; interaktive Pulvermischung AB Drug delivery to the lungs is known as the main application route to treat diseases like asthma or chronic obstructive pulmonary disease. Particles for lung penetration require aerodynamic particle sizes between 0.5 µm and 5.0 µm to provoke an effect. Dry powder formulations as used in this project provide improved long term stability when compared to liquid formulations. The well-established system of coarse carrier and small cohesive drug particles was applied in this work to overcome drug cohesiveness and facilitate dosing accuracy. This project was mainly focussing on the preparation of mannitol carrier and drug particles with controlled particle properties to discover the effects of those properties on particle-particle interactions and so on the resulting fine particle fraction – as the fraction of particles with an aerodynamic diameter below 5 µm gained by impaction analysis. Spray drying was used as method of choice for all substances used. A design of experiments was applied for the drying of mannitol. Drying experiments resulted in different qualities based on different rotation speeds of a rotary atomiser and different drying temperatures, resulting in particles of different sizes and morphologies. With this it was possible to illustrate the drying kinetics with respect to the temperature within droplet or early particle. Four hydrophilic and hydrophobic model drugs were spray dried with a commercially available spray drier. Resulting batches were blended with a choice of six mannitol batches. Aerodynamic characterisations exhibited carrier shape to have the main impact on drug dispersion, but illustrated different drugs to show different dependencies with respect to drug-to-drug and drug-to-carrier interactions. Apart from carrier shape, carrier and drug size were found to be important for accurate drug dispersion. This project gives a broad overview over particle-particle interactions between carrier and drug particles of various qualities during inhalation. PI Kiel ER