Complex carrier particles for respiratory drug delivery analysed with sequentially built DEM-simulation models

In this study the applicability of different tailor-made carrier particle geometries in interactive powder mixtures for respiratory drug delivery was analysed. Therefore, several numerical simulation models based on the discrete element method were used to give insight into the particle-particle interactions in the powder blend. A loading simulation for creating an interactive blend of the carrier particle with a model drug was performed. The resulting loaded carrier particles were used for consecutive particle-particle and particle-wall collision simulations representing the dispersion process of the drug in the air stream during the inhalation manoeuvre of a patient using the medication. Ten different complex carrier particle geometries were tested, each representing distinct features such as asymmetries, grooves, indentations and spikes. With a Design of Experiment approach, multiple different setups were compared statistically accounting for the high variability in particle movement during realistic inhalation of powder through an inhaler device. After the evaluation of 2700 individual simulations, the findings showed significant influences of the carrier geometry. As a main indicator of the performance, the detachment of the drug from the carrier particle's surface was evaluated. One particle, namely the Pharmacone, showed in particular superior performance. The Pharmacone is characterised by its spikes protruding from the main body. These spikes significantly influence the Pharmacone's movement during the collision either with another Pharmacone or with a flat wall and thus the detachment of the drug that covered the Pharmacone's surface prior to the collision.