In Vitro and In Silico Investigations on Drug Delivery in the Mouth-Throat Models with Handihaler®.

This work aimed to evaluate the relative inhalation parameters that affect the deposition of inhaled aerosols, including mouth-throat morphology, airflow rate, and initial condition of emitted particles. In vitro experiments were conducted using the US Pharmacopeia (USP) throat and a realistic mouth-throat (RMT) with Handihaler®. Then, in silico study of the gas-solid flow was performed by computational fluid dynamics and discrete phase method. Results indicated that aerosol deposition in RMT was higher compared to that in USP throat at an airflow rate of 30 L/min, with 33.16 ± 7.84% and 21.11 ± 7.1% lung deposition in USP throat and RMT models, respectively, which showed a better correlation with in vivo data from the literature. Increasing airflow rate resulted in better drug aerosolization, while the fine particle dose trend ascended before declining, with the peak value obtained at a flow rate of 40 L/min. Overall, the effect of geometrical variation was more significant. Additionally, in silico results demonstrated clearly that the initial conditions of the emitted particles from inhalers affected the subsequent deposition. Larger momentum possessed by the central aerosol jet entering the mouth directly led to stronger impaction, which resulted in the deposition in the front region of mouth-throat models. This study is beneficial to develop an in silico method to understand the underlying mechanisms of in vivo mouth-throat deposition.

DEM simulation of the local ordering of tetrahedral granular matter.

The formation and growth of local order clusters in a tetrahedral granular assembly driven by 3D mechanical vibration were captured in DEM (discrete element method) dynamic simulation using a multi-sphere model. Two important kinds of clusters, dimer and wagon wheel structures, were observed based on which the growth behavior and mechanism of each local cluster with different orientations/structures were investigated. The results show that during vibration, dimer clusters are formed first and then most of them grow into linear trimers and tetramers. Wagon wheel clusters are also frequently observed that grow into hexamers and, further, octamer and nonamer local clusters. Coordination number (CN) evolution indicates that the decrease of local mean CN can be regarded as the signal for the formation of local clusters in the tetrahedral particle packing system. Nematic order metric analysis shows that although the two basic structures (dimer and wagon wheel structures) grow into complex local clusters during packing densification, these local clusters are randomly distributed in the tetrahedral particle packing system. Stress analysis indicates that the dimer-based local clusters are mostly formed in the compaction state of the tetrahedral particle packing system during the vibrated packing densification process. In comparison, the wagon wheel-based local clusters need much stronger interaction forces from tetrahedral particles during vibrated packing densification.