Understanding the effects of inhaler resistance on particle deposition behaviour – A computational modelling study

Background and objective: Understanding the impact of inhaler resistance on particle transport and deposition in the human upper airway is essential for optimizing inhaler designs, thereby contributing to the enhancement of the therapeutic efficacy of inhaled drug delivery. This study demonstrates the potential effects of inhaler resistance on particle deposition characteristics in an anatomically realistic human oropharynx and the United States Pharmacopeia (USP) throat using computational fluid dynamics (CFD). Method: Magnetic resonance (MR) imaging was performed on a healthy volunteer biting on a small mockup inhaler mouthpiece. Three-dimensional geometry of the oropharynx and mouthpiece were reconstructed from the MR images. CFD simulations coupled with discrete phase modelling were conducted. Inhaled polydisperse particles under two different transient flow profiles with peak inspiratory flow rates (PIFR) of 30 L/min and 60 L/min were investigated. The effect of inhaler mouthpiece resistance was modelled as a porous medium by varying the initial resistance (Ri) and viscous resistance (Rv). Three resistance values, 0.02 kPa0.5minL−1, 0.035 kPa0.5minL−1 and 0.05 kPa0.5 minL−1, were simulated. The inhaler outlet velocity was set to be consistent across all models for both flow rate conditions to enable a meaningful comparison of models with different inhaler resistances. Result: The results from this study demonstrate that investigating the effect of inhaler resistance by solely relying on the USP throat model may yield misleading results. For the geometrically realistic oropharyngeal model, both the pressure and kinetic energy profiles at the mid-sagittal plane of the airway change dramatically when connected to a higher-resistance inhaler. In addition, the geometrically realistic oropharyngeal model appears to have a resistance threshold. When this threshold is surpassed, significant changes in flow dynamics become evident, which is not observed in the USP throat model. Furthermore, this study also reveals that the impact of inhaler resistance in a geometrically realistic throat model extends beyond the oral cavity and affects particle deposition downstream of the oral cavity, including the oropharynx region. Conclusion: Results from this study suggest that key mechanisms underpinning the working principles of inhaler resistance are intricately connected to their complex interaction with the pharynx geometry, which affects the local pressure, local variation in velocity and kinetic energy profile in the airway

Numerical analysis of airflow and particle deposition in multi-fidelity designs of nasal replicas following nasal administration

Background and Objective: An improved understanding of flow behaviour and particle deposition in the human nasal airway is useful for optimising drug delivery and assessing the implications of pollutants and toxin inhalation. The geometry of the human nasal cavity is inherently complex and presents challenges and manufacturing constraints in creating a geometrically realistic replica. Understanding how anatomical structures of the nasal airway affect flow will shed light on the mechanics underpinning flow regulation in the nasal pharynx and provide a means to interpret flow and particle deposition data conducted in a nasal replica or model that has reduced complexity in terms of their geometries. This study aims to elucidate the effects of sinus and reduced turbinate length on nasal flow and particle deposition efficiencies. Methods: A complete nasal airway with maxillary sinus was first reconstructed using magnetic resonance imaging (MRI) scans obtained from a healthy human volunteer. The basic model was then modified to produce a model without the sinus, and another with reduced turbinate length. Computational fluid dynamics (CFD) was used to simulate flow in the nasal cavity using transient flow profiles with peak flow rates of 15 L/min, 35 L/min and 55 L/min. Particle deposition was investigated using discrete phase modelling (DPM). Results: Results from this study show that simplifying the nasal cavity by removing the maxillary sinus and curved sections of the meatus only has a minor effect on airflow. By mapping the spatial distribution of monodisperse particles (10 μm) in the three models using a grid map that consists of 30 grids, this work highlights the specific nasal airway locations where deposition efficiencies are highest, as observed within a single grid. It also shows that lower peak flow rates result in higher deposition differences in terms of location and deposition quantity, among the models. The highest difference in particle deposition among the three nasal models is ∼10%, and this is observed at the beginning of the middle meatus and the end of the pharynx, but is only limited to the 15 L/min peak flow rate case. Further work demonstrating how the outcome may be affected by a wider range of particle sizes, less specific to the pharmaceutical industries, is warranted. Conclusion: A physical replica manufactured without sections of the middle meatus could still be adequate in producing useful data on the deposition efficiencies associated with an intranasal drug formulation and its delivery device

Characteristics of electrohydrodynamic roll structures in laminar planar Couette flow

The behaviour of an incompressible dielectric liquid subjected to a laminar planar Couette flow with unipolar charge injection is investigated numerically in two dimensions. The computations show new morphological characteristics of roll structures that arise in this forced electro-convection problem. The charge and velocity magnitude distributions between the two parallel electrodes are discussed as a function of the top wall velocity and the EHD Rayleigh number, T for the case of strong charge injection. A wide enough parametric space is investigated such that the observed EHD roll structures progress through three regimes. These regimes are defined by the presence of a single or double-roll free convective structure as observed elsewhere (Vazquez et al 2008 J. Phys. D 41 175303), a sheared or stretched roll structure, and finally by a regime where the perpendicular velocity gradient is sufficient to prevent the generation of a roll. These three regimes have been delineated as a function of the wall to ionic drift velocity UW/κE, and the T number. In the stretched regime, an increase in UW/κE can reduce charge and momentum fluctuations whilst in parallel de-stratify charge in the region between the two electrodes. The stretched roll regime is also characterised by a substantial influence of UW/κE on the steady development time, however in the traditional non-stretched roll structure regime, no influence of UW/κE on the development time is noted.13 page(s

An experimental study of transient effects in a pulsed, piloted, non-premixed turbulent jet flame

This paper reports an experimental investigation of the effects of pulsing a pilot-stabilised turbulent non-premixed turbulent. The pulse consists of a burst of fuel that induces a sudden increase in the otherwise steady velocity from a value where the flame is fully burning to a level higher than the blow-off velocity. The duration of the pulse is 10ms. The transient velocity field is measured along with the high-speed imaging of LIF-OH as well as OH-chemiluminescence (OH*) at various axial locations in the jet. It is found that, with downstream distance, the pulse width is slightly shorter and the peak velocity of the pulse decays at a faster rate than the normal velocity decay of the fluid. The disturbance travels along the jet at the convective velocity. Image sequences of LIF-OH show that, in the region extending from about x/D∼15-35, the flame extinguishes totally for a duration similar to the pulse width. These findings support and extend findings reported earlier by the same group [1].4 page(s

Spray characterization of ethanol and saturated biodiesels of different carbon chain lengths

This paper examines the flame appearance, non-reacting and reacting spray of ethanol, a short and a medium carbon chain length biodiesel in a co-flow burner using digital images and Phase Doppler Anemometer (PDA). The effects of fuel chemical structures on flame luminous location, dispersion level, number droplet distribution, and droplet velocity decay rate are investigated. Some differences in luminous locations in the flames of these fuels are observed. The medium chain length biodiesel shows the lowest luminous locations in all flame conditions; at the dense spray zone, the short chain length biofuel has the highest luminous locations while this belongs to ethanol at the dilute spray zone. Non-reacting spray dispersion levels of the medium chain length biofuel are higher compared to those of its counterparts. Velocity decay rates of non-reacting droplets are much higher with respect to those of reacting ones, especially at downstream locations.4 page(s

A New approach in characterizing secondary-breakup regimes for newtonian liquids

An image processing technique developed earlier using backlit shadowgraph for primary and secondary atomization study has been extended in this work to investigate the breakup evolution of a broad range of biodiesels, ethanol and fossil diesel. The backlit system uses a high speed CMOS camera in conjunction with a long distance microscope objective lens with the aid of a diffused light beam generated from a diode stack high-speed Nd-YAG laser. In the current work, a new approach of using the spatial gradient of area of fragment shapes is developed to improve understanding of the droplet-to-fragment and fragment-to-fragment breakup processes. A definition of breakup length is given here as the length between the initial location of the parent droplet and the location where the spatial gradient of area of ligaments and unbroken objects becomes close to zero. The non-dimensional breakup-time characteristic is then estimated using the measured breakup length and an appropriate velocity scale. This quantitative approach is capable of comparing the breakup time amongst different fuels and could be used to improve current breakup-time models. The trend of breakup-time observed in this study matches quite well with that reported by Pilch and Erdman [1]. The time however, is one order of magnitude shorter than that noticed by Pilch and Erdman. This is attributed to the difference in the breakup time definitions and the experimental techniques used in Pilch and Erdman’s work and those in this study, as has also been observed elsewhere [1].4 page(s