Flow and Particle Modelling of Dry Powder Inhalers: Methodologies, Recent Development and Emerging Applications

Abstract

Dry powder inhaler (DPI) is a device used to deliver a drug in dry powder form to the lungs. A wide range of DPI products is currently available, with the choice of DPI device largely depending on the dose, dosing frequency and powder properties of formulations. Computational fluid dynamics (CFD), together with various particle motion modelling tools, such as discrete particle methods (DPM) and discrete element methods (DEM), have been increasingly used to optimise DPI design by revealing the details of flow patterns, particle trajectories, de-agglomerations and depositions within the device and the delivery paths. This review article focuses on the development of the modelling methodologies of flow and particle behaviours in DPI devices and their applications to device design in several emerging fields. Various modelling methods, including the most recent multi-scale approaches, are covered and the latest simulation studies of different devices are summarised and critically assessed. The potential and effectiveness of the modelling tools in optimising designs of emerging DPI devices are specifically discussed, such as those with the features of high-dose, pediatric patient compatibility and independency of patients' inhalation manoeuvres. Lastly, we summarise the challenges that remain to be addressed in DPI-related fluid and particle modelling and provide our thoughts on future research direction in this field.

Keywords: computational fluid dynamics (CFD); computational modelling; discrete element methods (DEM); dry powder inhalers (DPI); inhalation therapy; pulmonary drug delivery.

Figure 1

Schematics of dry powder inhaler (DPI) dispersion mechanisms.

Figure 2

Calculated velocity profile (a) and turbulence scale (b) of an Aerolizer^® using RANS with k-ε SST model. Reproduced with permission from [8], Elsevier, 2004.

Figure 3

Schematic of a multidose dry powder inhaler (a) and calculated particle deposition (particle sizes from left to right are 1 μm, 2 μm and 5 μm, respectively) in the device (b) via a simple particle trajectory modelling. Reproduced with permission from [13], Elsevier, 2013.

Figure 4

Breakage pattern of agglomerate due to collision simulated by Tong et al. [37] at the progression time. Reproduced with permission from [37], Elsevier, 2016.

Figure 5

(a) Schematic of an Aerolizer^® inhaler with a pierced capsule and (b) streamlines in the capsule chamber. Reproduced/Adapted with permission from [10], Elsevier, 2019.

Figure 6

Schematic of a DPI device layout with a bypass channel to achieve flow independency.