Prediction of drug particle transport in a dry powder inhaler using Rocky DEM

Jianan Zhao and Yu Feng
School of Chemical Engineering, Oklahoma State University

Pulmonary drug delivery devices such as dry powder inhalers (DPIs) have been widely used to deliver an efficacious dose of active pharmaceutical ingredients (APIs) into the targeted respiratory system. Rocky DEM multiphysics simulation provides significant value for optimizing the design of DPIs as well as demonstrating the bioequivalence (BE) of generic DPI products, since Rocky has the unique capability to describe the underlying physical and chemical mechanisms of the drug transport and interactions, noninvasively. Compared with in vitro tests, numerical simulation is less expensive and time-consuming while providing accurate results for reducing the research/development cycle duration of DPI product innovations.

The advantages of CFD-DEM models

Rocky DEM offers an inclusive list of particle shapes combined with advanced laws of fluid force that accurately predict particle transport dynamics, especially when the particles are in anisotropic shapes, e.g., fiber-like shapes. In addition, validated contact detection models precisely capture the interaction among particles with complex shapes.
During the release and emission inside DPIs, particle-particle interaction forces, i.e., the van der Waals and electrostatic forces, play a vital role in drug particle transport and determine the emitted aerodynamic size distribution entering a human mouth, These forces have a significant impact on the evaluation of the effective delivered dose to the lung sites designated for lung disease treatment. For this purpose, Rocky DEM brings multiple adhesive force models so that engineers will only need to define the surface energy parameter to capture the material’s adhesive/cohesive behavior.

The one-way coupled CFD-DEM can predict drug particle dynamics in a DPI

Figure 1 shows the geometry of the dry powder inhaler device and its polyhedron mesh with six hexahedron prisms near the wall. The mesh independence test was performed to determine the final mesh with the optimized balance between computational accuracy and efficiency. Details about the mesh independence test and the final mesh specifications are shown in Figure 2.

Reconstructed DPI geometry and the hybrid polyhedral mesh, including the flow channel, grid, and capsule with pierced holes
Figure 1. Reconstructed DPI geometry and the hybrid polyhedral mesh, including the flow channel, grid, and capsule with pierced holes.
Mesh independence test-based airflow field simulations
Figure 2. Mesh independence test-based airflow field simulations under an actuated flow rate of 30 L/min.

The highlighted features involved in the current CFD-DEM simulations are summarized as follows:

The one-way coupling algorithm between CFD and DEM

For the current case study, the one-way coupling method is employed for the interactions between particles and the airflow. The CFD simulation is performed using ANSYS Fluent to generate steady-state airflow fields. The airflow data were then imported into Rocky DEM to calculate fluid-particle and particle-particle interactions and the resultant particle trajectories in the flow channel shown in Figure 1.

Customized non-spherical particle shapes

Users can easily define particles with various sizes and shapes in Rocky DEM, including rigid and flexible custom convex and concave shapes, flexible fibers, and shell particles. In this pilot study, sphero-cylindrical particles were simulated, and the particle transport dynamics were compared with spherical particles. Specifically, the sphero-cylindrical particles have a vertical aspect ratio of 2.0 and an equivalent sphere diameter of 3 μm, which is the same as the spherical particles.

Particle-particle interaction

Rocky DEM can explicitly model the transient forces and torques acting on individual particles. Contact detection and contact forces can be calculated between arbitrarily shaped particles. The Hertz-Mindlin (H-M) model with Johnson-Kendall-Roberts (JKR) cohesion was employed for calculating the inter-particulate van der Waals and electrostatic forces.

Post-processing using Rocky DEM

Rocky DEM allows users to efficiently analyze their simulation results, especially for particle contact and trajectories. Users can click the Particle Time Selection Process to store the particle information (position, velocities, etc.), particle-particle interactions, and particle-device interactions.

By using customized Python scripts, users can export and analyze particle properties. For example, users can export aerodynamic particle size distributions (APSDs) emitted at the mouthpiece opening as the input boundary condition for further investigation of the pharmaceutical particles’ transport in human airways.

Figure 3 shows the airflow velocity magnitude distribution at the sagittal plane in the DPI and the comparison of particle transport dynamics at time t = 0.001 s between spherical and sphero-cylindrical particles. The comparison between two cases shown in Figure 3 indicates that, compared with sphero-cylindrical particles, spherical particles are better at following the airflow transport faster than the elongated particles with different particle-particle collision frequencies. Therefore, it can be observed that the particle shape effects can significantly influence the particle dispersions and will determine the emitted APSDs.

Comparisons of particle transport dynamics
Figure 3. Comparisons of particle transport dynamics at time t = 0.001 s between 3-μm spherical and sphero-cylindrical particles (vertical aspect ratio=2.0) with an equivalent diameter of 3 μm.

GPU Speed-up Test

Rocky DEM state-of-the-art multi-core and multi-GPU engine utilization enables enhanced computational efficiency. Three NVIDIA Quadro RTX 6000 GPUs were equipped and employed testing the speed-up using Rocky DEM. Details are listed in Table 1 for the DEM particle setup and the performance of multiple GPUs solver applied in this pilot study.

Table 1. Rocky DEM particle setup and multiple GPUs solver performance details.
Table of Rocky DEM particle setup and multiple GPUs solver performance details

Future Work

For carrier-based dry powder dynamics, it is necessary to study the particle shape effects on the agglomeration/de-agglomeration effects and the resultant differences in the lung depositions. The adhesive force parameters in Rocky DEM will be optimized by the experimentally measured surface energy using Atomic Force Microscopy (AFM).

Acknowledgment

The use of Rocky DEM (ESSS, Woburn, MA) as part of the ESSS-CBBL academic partnership agreement is gratefully acknowledged (Dr. Rahul Bharadwaj, Vice President, Engineering and Business Development).

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