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.

Comparison between spray drying and freeze drying techniques for the preparation of microparticles for delivery via a dry powder inhaler to treat cystic fibrosis

“…Our particles were within the said range [26]. Various studies have identified that particles of sizes between 1-5 µm have the ideal deposition pattern in the airways [27]. However, particles with sizes on either side of the proposed range have a cohesiveness that is not perfect for aerosolization [28].…”

Comparative Assessment of In Vitro and In Silico Methods for Aerodynamic Characterization of Powders for Inhalation

“…CFD modeling for various DPI devices (Aerolizer ® , Turbuhaler ® , Twincer ® , Handihaler ® , Accuhaler ® , Multihaler ® , etc.) has already been described [54], but to the best of our knowledge the CFD-DPM model of RS01 ® inhaler has not been published in the available literature.…”

“…Overall, some correlation between in vitro and in silico CFD results has been detected [48][49][50][51][52][53], but there is a need for additional comparative assessment of CFD tools in relation to the in vitro methods to evaluate the applicability of CFD in the research and development of various DPI formulations. A recent review study of Zheng et al (2021) also concluded that more direct comparison between the simulated and experimental results is necessary to improve the prediction accuracy of in silico tools [54].…”

Numerical Modeling of Particle Dynamics Inside a Dry Powder Inhaler

“…In order to be successfully delivered and deposited in the lungs, the particles should have an aerodynamic diameter of 0.5 µm to 5 µm, while those with an aerodynamic diameter of less than 3 µm have the chance of reaching the respiratory zone [2]. The particles of such a small diameter generated by the inhaler are very cohesive and can either form drug-only agglomerates or can be attached to larger carrier particles [3,4]. In order for the particles to be effectively transported and deposited in the lungs, processes of particle dispersion and deaggregation are required.…”