A counter-swirl design concept for dry powder inhalers.

A swirling airflow is incorporated in several dry powder inhalers (DPIs) for effective powder de-agglomeration. This commonly requires the use of a flow-straightening grid in the DPI to reduce drug deposition loss caused by large lateral spreading of the emerging aerosol. Here, we propose a novel grid-free DPI design concept that improves the aerosol flow characteristics and reduces the aforementioned drug loss. The basis of this design is the implementation of a secondary airflow that swirls in the opposite direction (counter-swirl) to that of a primary swirling airflow. In-vitro deposition, computational fluid dynamics simulations and particle image velocimetry measurements are used to evaluate the counter-swirl DPI aerosol performance and flow characteristics. In comparison with a baseline-DPI that has only a primary swirling airflow, the counter-swirl DPI has 20% less deposition of the emitted drug dose in the induction port and pre-separator of a next generation impactor (NGI). This occurs as a result of the lower flow-swirl generated from the counter-swirl DPI which eliminates the axial reverse flow outside of the mouthpiece and substantially reduces lateral spreading in the exiting aerosol. Modifications to the counter-swirl DPI design were made to prevent drug loss from the secondary airflow tangential inlets, which involved the addition of wall perforations in the tangential inlets and the separation of the primary and secondary swirling airflows by an annular channel. These modified DPI devices were successful in that aspect but had higher flow-swirl than that in the counter-swirl DPI and thus had higher drug mass retained in the device and deposited in the induction port and pre-separator of the NGI. The fine particle fraction in the aerosols generated from all the counter-swirl-based DPIs and the baseline-DPI are found to be statistically similar to each other.

Advances in soft mist inhalers.

INTRODUCTION: Soft mist inhalers (SMIs) are propellant-free inhalers that utilize mechanical power to deliver single or multiple doses of inhalable drug aerosols in the form of a slow mist to patients. Compared to traditional inhalers, SMIs allow for a longer and slower release of aerosol with a smaller ballistic effect, leading to a limited loss in the oropharyngeal area, whilst requiring little coordination of actuation and inhalation by patients. Currently, the Respimat® is the only commercially available SMI, with several others in different stages of preclinical and clinical development. AREAS COVERED: The primary purpose of this review is to critically assess recent advances in SMIs for the delivery of inhaled therapeutics. EXPERT OPINION: Advanced particle formulations, such as nanoparticles which target specific areas of the lung, Biologics, such as vaccines, proteins, and antibodies (which are sensitive to aerosolization), are expected to be generally delivered by SMIs. Furthermore, repurposed drugs are expected to constitute a large share of future formulations to be delivered by SMIs. SMIs can also be employed for the delivery of formulations that target systemic diseases. Finally, digitalizing SMIs would improve patient adherence and provide clinicians with fundamental insights into patients' treatment progress.

On the Use of Computational Fluid Dynamics (CFD) Modelling to Design Improved Dry Powder Inhalers.

PURPOSE: Computational Fluid Dynamics (CFD) simulations are performed to investigate the impact of adding a grid to a two-inlet dry powder inhaler (DPI). The purpose of the paper is to show the importance of the correct choice of closure model and modeling approach, as well as to perform validation against particle dispersion data obtained from in-vitro studies and flow velocity data obtained from particle image velocimetry (PIV) experiments. METHODS: CFD simulations are performed using the Ansys Fluent 2020R1 software package. Two RANS turbulence models (realisable k - ε and k - ω SST) and the Stress Blended Eddy Simulation (SBES) models are considered. Lagrangian particle tracking for both carrier and fine particles is also performed. RESULTS: Excellent comparison with the PIV data is found for the SBES approach and the particle tracking data are consistent with the dispersion results, given the simplicity of the assumptions made. CONCLUSIONS: This work shows the importance of selecting the correct turbulence modelling approach and boundary conditions to obtain good agreement with PIV data for the flow-field exiting the device. With this validated, the model can be used with much higher confidence to explore the fluid and particle dynamics within the device.

In-vitro and particle image velocimetry studies of dry powder inhalers.

Inhalation drug delivery has seen a swift rise in the use of dry powder inhalers (DPIs) to treat chronic respiratory conditions. However, universal adoption of DPIs has been restrained due to their low efficiencies and significant drug losses in the mouth-throat region. Aerosol efficiency of DPIs is closely related to the fluid-dynamics characteristics of the inhalation flow generated from the devices, which in turn are influenced by the device design. In-vitro and particle image velocimetry (PIV) have been used in this study to assess the aerosol performance of a model carrier formulation delivered by DPI devices and to investigate their flow characteristics. Four DPI device models, with modification to their tangential inlets and addition of a grid, have been explored. Similar aerosol performances were observed for all four device models, with FPF larger than 50%, indicating desirable lung deposition. A high swirling and recirculating jet-flow emerging from the mouthpiece of the DPI models without the grid was observed, which contributed to particle deposition in the throat. DPI models where the grid was present showed a straightened outflow without undesired lateral spreading, that reduced particle deposition in the throat and mass retention in the device. These findings demonstrate that PIV measurements strengthen in-vitro evaluation and can be jointly used to develop high-performance DPIs.