Mouth-throat Model Research Articles

Adjoint Solver-Based Analysis of Mouth–Tongue Morphologies on Vapor Deposition in the Upper Airway

Even though inhalation dosimetry is determined by three factors (i.e., breathing, aerosols, and the respiratory tract), the first two categories have been more widely studied than the last. Both breathing and aerosols are quantitative variables that can be easily changed, while respiratory airway morphologies are difficult to reconstruct, modify, and quantify. Although several methods are available for model reconstruction and modification, developing an anatomically accurate airway model and morphing it to various physiological conditions remains labor-intensive and technically challenging. The objective of this study is to explore the feasibility of using an adjoint–CFD model to understand airway shape effects on vapor deposition and control vapor flux into the lung. A mouth–throat model was used, with the shape of the mouth and tongue being automatically varied via adjoint morphing and the vapor transport being simulated using ANSYS Fluent coupled with a wall absorption model. Two chemicals with varying adsorption rates, Acetaldehyde and Benzene, were considered, which exhibited large differences in dosimetry sensitivity to airway shapes. For both chemicals, the maximal possible morphing was first identified and then morphology parametric studies were conducted. Results show that changing the mouth–tongue shape can alter the oral filtration by 3.2% for Acetaldehyde and 0.27% for Benzene under a given inhalation condition. The front tongue exerts a significant impact on all cases considered, while the impact of other regions varies among cases. This study demonstrates that the hybrid adjoint–CFD approach can be a practical and efficient method to investigate morphology-associated variability in the dosimetry of vapors and nanomedicines under steady inhalation.

Numerical study on the effect of the realistic mouth-inhaler positions on orally inhaled drug delivery in pediatric intersubject upper airways

The relative position between the pediatric upper airway and the inhalation device during real inhalation administration has significant effects on the delivery efficiency of orally inhaled drugs. Morphological variability plays an important role in this process. However, the mouth-throat differences between adults and children were usually neglected because most of the commercial inhalation devices currently are designed for adults or older adolescents. The main objective of this study is to investigate these effects by four realistic pediatric mouth-throat (RMT) geometries. In addition, an idealized mouth-throat (IMT) model was developed to validate the numerical model and to compare with the RMT models. Computational fluid dynamics (CFD) simulations were performed to investigate the flow pattern and deposition pattern in these models and the results were compared with the cascade impactor experiments, replica experiments and in vivo results. No significant correlation (p > 0.1) between the relative position parameters and inhaler insertion depth can be noticed among the RMT models. Notably, significant variability in the inhaler posture was observed in RMT models, especially for the S4 model. Airflow structure shows that the RMT model has a complex onset of turbulence, reverse flow and subsequently vortex formation when compared with the IMT model. The oral cavity is the region with the largest deposition fraction (DF) and deposition efficiency (DE). The DF and DE of the oral cavity are negatively correlated to the position parameter (Lm) when mass median aerodynamic diameter (MMAD) of indacaterol 150 μg was utilized as the input particle parameter. The relative position between the inhaler and oral cavity has significant effects on the particle transport and deposition. Furthermore, in silico results overestimated the lung deposition in comparison to the in vivo and experimental results when MMAD was used as input. To resolve the disparity between the in silico and in vivo results, a modified prediction method based on the cascade impactor and original in silico results was proposed and a good correlation of the relative contribution of pulmonary absorption to total systemic exposure (flung) was found between the predicted and observed results. The findings of present work will provide useful information in understanding the particle transport and deposition in the pediatric airways for the design of inhaler.

The effects of aerosol concentration on the evolution, transport, and deposition of hygroscopic droplets in the highly idealized MT model: A numerical study

Inhalation therapy is widely used to treat various respiratory diseases. Nebulizers have been widely adopted due to their ease of operation, high drug delivery efficiency, and low residual volume. Traditional studies on drug delivery in the respiratory tract typically use a one-way coupled method to track drug transport and deposition for non-hygroscopic drug particles. However, neglecting the concentration of nebulized hygroscopic droplet aerosols can lead to significant discrepancies in the deposition efficiency (DE) of nebulized drugs in the airways. To investigate the effect of different nebulization rates on the evolution, transport, and deposition of droplets, a highly idealized mouth-throat (MT) model was selected as a testbed for the in silico trials of drug delivery to the respiratory tract. The interaction between continuous and discrete phases was modeled using a two-way coupled model of highly concentrated droplet aerosol-water vapor interaction, innovated by the particle parcel method. The effects of different coupling methods and boundary conditions on the average droplet diameter and droplet deposition distribution pattern at the outlet of the MT model were compared using a computational fluid dynamics (CFD) method. Simulation results indicate that neglecting the effect of water vapor evaporated from the droplets on the relative humidity (RH) in the oral cavity could lead to a 2.2-fold prediction error of the average droplet diameter at the outlet of the MT model for a conventional nebulization rate of 0.386 g/min. As the nebulization rate increases, the difference in the predicted average droplet diameter at the outlet of the MT model between the one-way coupled method and the two-way coupled method also increases. Increasing the nebulization rate during inhalation therapy could lead to incomplete evaporation of drug droplets, resulting in deposition of larger diameter drug droplets in the oral cavity. In contrast, a lower nebulization rate can reduce the droplet diameter at the outlet of the MT model, allowing it to enter deeper airways.

Effects of vocal fold adduction on the particle deposition in the glottis: A numerical analysis and in vitro assessment

BackgroundThe efficacy of inhalation therapy depends on the drug deposition in the human respiratory tract. This study investigates the effects of vocal fold adduction on the particle deposition in the glottis. MethodsA realistic mouth-throat (MT) geometry was built based on CT images of a healthy adult (MT-A). Mild (MT-B) and great (MT-C) vocal fold (VF) adduction were incorporated in the original model. Monodisperse particles range in size from 3 to 12 μm were simulated at inspiration flow rates of 15, 30 and 45 L per minute (LPM). The regional deposition of drug aerosols was performed in 3D-printed models and quantified using high-performance liquid chromatography. ResultsBoth the numerical analysis and in vitro experiments show that most particles are deposited in the mouth, pharynx and supraglottis, while few are deposited in the glottis and subglottis. For most cases in MT-A, the particle quantity in glottis is lower than 0.02 N/mm2 at 15 and 30 LPM while they increase dramatically at 45 LPM. It peaked at 0.347 N/mm2 for 5-μm particles at 45 LPM in MT-B and 2.324 N/mm2 for 6-μm particles at 30 LPM in MT-C. The lowest drug mass faction in the glottis in vitro were found at 15 LPM for MT-A and MT-C, and at 30 LPM for MT-B, whereas it peaked at 45 LPM for all MT models, 0.71% in MT-A, 1.16% in MT-B, and 2.53% in MT-C, respectively. ConclusionBased on the results of this study, larger particles are more likely to be deposited in the oral cavity, oropharynx, and supraglottis than in the glottis. However, particle deposition in the glottis generally increases with VF adduction and greater inspiratory flow rates.

Effects of vocal fold lesions on particle deposition in a mouth-throat model: A numerical study

ObjectiveDysphonia is very common worldwide and aerosol drug inhalation is an important treatment for patients with dysphonia. This study aimed to explore the effects of vocal fold (VF) lesions on the particle deposition pattern using computational modeling. MethodsA realistic mouth-throat (MT) model of a healthy adult was constructed based on computed tomography images. Small and large vocal fold lesions were incorporated in the original model. A steady inhalation flowrate of 15 and 30 liter per minute (LPM) was used as the velocity inlet and monodisperse particles with diameters of 5 to 10 µm were simulated. ResultsParticles of larger size are more likely to be deposited in MT models, most of them distributed in oral cavity, oropharynx and supraglottis. The ideal sizes at 30 LPM ranged over 7-10 µm for healthy VFs and 6-8 µm for VF lesions. The best sizes at 15 LPM ranged over 6-8 µm for healthy VFs and 8-9 µm for VF lesions. ConclusionBased on this study, VF lesions influence the deposition pattern in the glottis obviously. The ideal sizes differ at the flow rates of 15 and 30 LPM.

In vitro-in silico correlation of three-dimensional turbulent flows in an idealized mouth-throat model.

There exists an ongoing need to improve the validity and accuracy of computational fluid dynamics (CFD) simulations of turbulent airflows in the extra-thoracic and upper airways. Yet, a knowledge gap remains in providing experimentally-resolved 3D flow benchmarks with sufficient data density and completeness for useful comparison with widely-employed numerical schemes. Motivated by such shortcomings, the present work details to the best of our knowledge the first attempt to deliver in vitro-in silico correlations of 3D respiratory airflows in a generalized mouth-throat model and thereby assess the performance of Large Eddy Simulations (LES) and Reynolds-Averaged Numerical Simulations (RANS). Numerical predictions are compared against 3D volumetric flow measurements using Tomographic Particle Image Velocimetry (TPIV) at three steady inhalation flowrates varying from shallow to deep inhalation conditions. We find that a RANS k-ω SST model adequately predicts velocity flow patterns for Reynolds numbers spanning 1'500 to 7'000, supporting results in close proximity to a more computationally-expensive LES model. Yet, RANS significantly underestimates turbulent kinetic energy (TKE), thus underlining the advantages of LES as a higher-order turbulence modeling scheme. In an effort to bridge future endevours across respiratory research disciplines, we provide end users with the present in vitro-in silico correlation data for improved predictive CFD models towards inhalation therapy and therapeutic or toxic dosimetry endpoints.

Effects of device settings and e-liquid characteristics on mouth-throat losses of nicotine delivered with electronic nicotine delivery systems (ENDS)

Currently it is not fully understood how the device settings and electronic liquid (e-liquid) composition, including their form of nicotine content, impact mouth and throat losses, and potentially lead to the variations in total nicotine delivery to the human lungs. An in situ size assessment method was developed for real-time measurements at the mouthpiece and outlet of a biorelevant mouth-throat to account for the dynamic nature of the aerosol. The aerosol size, temperature, and delivery through the mouth-throat replica and the exhaled aerosol between the puff intervals were measured at different wattages using various e-liquid compositions. The effects of body temperature and humidity on aerosol size and nicotine delivery were also explored to evaluate the importance of considering realistic in vivo conditions in in vitro measurements. Notably, in vitro tests with body temperature and humidity in mouth-throat model vs room conditions, resulted in larger aerosol size at the end of the throat (Dv50 = 5.83 ± 0.33 μm vs 3.05 ± 0.15 μm), significantly higher thoracic nicotine delivery (>90% vs 50–85%) potentially due to the lower exhaled amount (<10% vs 15–50%). Besides, higher VG/PG ratios resulted in significantly lower exhaled amount and higher mouth-throat nicotine deposition. One of the main outcomes of the study was finding significantly lower exhaled amount and higher thoracic nicotine delivery with nicotine salt form vs free-base. Considering body temperature and humidity also showed significant enhancement in nicotine delivery, so it is essential to account for biorelevant experimental conditions in benchtop testing.

The effects of temperature and humidity on the deposition of nebulized droplet in an idealized mouth-throat model

Inhalation therapy is a practical approach to treat respiratory diseases. Vibrating mesh nebulizer (VMN), a device for inhalation therapy, is favored for its advantages, such as portability and noiselessness. The droplet deposition experiment using the VMN was carried out in an idealized mouth-throat (MT) model. This study used the 0.9% w/v concentration of nebulized sodium chloride (NaCl) droplet to measure the deposition fraction (DF). The inhalation flow rates were changed under two different temperature and humidity conditions, and the variation of droplet DFs as a function of inertial parameters was obtained under different inhalation flow rate conditions. The results show that the DF first decreases and then increases with the increasing inertial parameter, which is distinctly different from previous conclusions for dry powder or particle experiments and simulations. It indicates that the droplet evaporation substantially affects the transport and deposition. The results also show that increasing the mass fraction of water vapor in the air increases droplet DF in the airway.

Evaporation Affects the In Vitro Deposition of Nebulized Droplet in an Idealized Mouth-Throat Model

Nebulizer is one of inhalation therapy’s most widely used aerosol generation devices. Nowadays, the vibrating mesh nebulizer has become popular owing to its compactness and noiselessness. In this study, an experimental system is proposed to measure the deposition fraction (DF) of nebulized sodium chloride (NaCl) droplets in an idealized mouth-throat airway model. The results show that before the DF increases to 58.6% with an increasing flow rate to 60 L/min, there is a decrease in DF from 42.4% to 15.5% when the inhalation flow rate increases from 15 to 22.5 L/min for a normal saline solution. These results substantially differ from the conclusions of dry powder or particle experiments and simulations, which monotonously increases with increasing inhalation flow rate. This suggests that droplet evaporation during aerosol generation and transport in the airway plays an important role. The experiment also showed that droplets generated from solutions with a higher NaCl concentration have higher DFs.

Flow Patterns and Particle Residence Times in the Oral Cavity during Inhaled Drug Delivery.

Pulmonary drug delivery aims to deliver particles deep into the lungs, bypassing the mouth–throat airway geometry. However, micron particles under high flow rates are susceptible to inertial impaction on anatomical sites that serve as a defense system to filter and prevent foreign particles from entering the lungs. The aim of this study was to understand particle aerodynamics and its possible deposition in the mouth–throat airway that inhibits pulmonary drug delivery. In this study, we present an analysis of the aerodynamics of inhaled particles inside a patient-specific mouth–throat model generated from MRI scans. Computational Fluid Dynamics with a Discrete Phase Model for tracking particles was used to characterize the airflow patterns for a constant inhalation flow rate of 30 L/min. Monodisperse particles with diameters of 7 m to 26 m were introduced to the domain within a 3 cm-diameter sphere in front of the oral cavity. The main outcomes of this study showed that the time taken for particle deposition to occur was 0.5 s; a narrow stream of particles (medially and superiorly) were transported by the flow field; larger particles > 20 m deposited onto the oropharnyx, while smaller particles < 12 m were more disperse throughout the oral cavity and navigated the curved geometry and laryngeal jet to escape through the tracheal outlet. It was concluded that at a flow rate of 30 L/min the particle diameters depositing on the larynx and trachea in this specific patient model are likely to be in the range of 7 m to 16 m. Particles larger than 16 m primarily deposited on the oropharynx.

In Vitro and In Silico Investigations on Drug Delivery in the Mouth-Throat Models with Handihaler®.

This work aimed to evaluate the relative inhalation parameters that affect the deposition of inhaled aerosols, including mouth-throat morphology, airflow rate, and initial condition of emitted particles. In vitro experiments were conducted using the US Pharmacopeia (USP) throat and a realistic mouth-throat (RMT) with Handihaler®. Then, in silico study of the gas-solid flow was performed by computational fluid dynamics and discrete phase method. Results indicated that aerosol deposition in RMT was higher compared to that in USP throat at an airflow rate of 30 L/min, with 33.16 ± 7.84% and 21.11 ± 7.1% lung deposition in USP throat and RMT models, respectively, which showed a better correlation with in vivo data from the literature. Increasing airflow rate resulted in better drug aerosolization, while the fine particle dose trend ascended before declining, with the peak value obtained at a flow rate of 40 L/min. Overall, the effect of geometrical variation was more significant. Additionally, in silico results demonstrated clearly that the initial conditions of the emitted particles from inhalers affected the subsequent deposition. Larger momentum possessed by the central aerosol jet entering the mouth directly led to stronger impaction, which resulted in the deposition in the front region of mouth-throat models. This study is beneficial to develop an in silico method to understand the underlying mechanisms of in vivo mouth-throat deposition.

How Nanoparticle Aerosols Transport through Multi-Stenosis Sections of Upper Airways: A CFD-DPM Modelling

Airway stenosis is a global respiratory health problem that is caused by airway injury, endotracheal intubation, malignant tumor, lung aging, or autoimmune diseases. A precise understanding of the airflow dynamics and pharmaceutical aerosol transport through the multi-stenosis airways is vital for targeted drug delivery, and is missing from the literature. The object of this study primarily relates to behaviors and nanoparticle transport through the multi-stenosis sections of the trachea and upper airways. The combination of a CT-based mouth–throat model and Weibel’s model was adopted in the ANSYS FLUENT solver for the numerical simulation of the Euler–Lagrange (E-L) method. Comprehensive grid refinement and validation were performed. The results from this study indicated that, for all flow rates, a higher velocity was usually found in the stenosis section. The maximum velocity was found in the stenosis section having a 75% reduction, followed by the stenosis section having a 50% reduction. Increasing flow rate resulted in higher wall shear stress, especially in stenosis sections. The highest pressure was found in the mouth–throat section for all flow rates. The lowest pressure was usually found in stenosis sections, especially in the third generation. Particle escape rate was dependent on flow rate and inversely dependent on particle size. The overall deposition efficiency was observed to be significantly higher in the mouth–throat and stenosis sections compared to other areas. However, this was proven to be only the case for a particle size of 1 nm. Moreover, smaller nanoparticles were usually trapped in the mouth–throat section, whereas larger nanoparticle sizes escaped through the lower airways from the left side of the lung; this accounted for approximately 50% of the total injected particles, and 36% escaped from the right side. The findings of this study can improve the comprehensive understanding of airflow patterns and nanoparticle deposition. This would be beneficial in work with polydisperse particle deposition for treatment of comprehensive stenosis with specific drugs under various disease conditions.

LES study on the impact of airway deformation on the airflow structures in the idealized mouth–throat model

To investigate the impacts of upper airway deformation on the airflow structures, the airflow fields in the trachea are simulated using three geometrical models considering three different levels of airway deformations. Structured grids are used to create the high-quality grids. Large eddy simulation with the Smagorinsky sub-grid model is adopted to solve the three-dimensional in-compressible Navier–Stokes equations using the solver pisoFoam in the open-source CFD software OpenFOAM. The numerical results demonstrate that the airway deformation influences the main airflow structures depending on the deformation level. Particularly, it slightly impacts on the laryngeal jet such as the profile and the strength of laryngeal jet. The strength of the laryngeal jet increases slightly for the heavy deformation. In contrast, it impacts on the recirculation zone, secondary vortices, and turbulent kinetic energy more obviously. The increasing airway deformation will produce stronger secondary flow, smaller recirculation zone, and weaker turbulent kinetic energy. The turbulence intensity distribution varies as well. The obviously impacted flow region is mainly within the region of one to six tracheal diameters downstream the glottis.

Numerical study on the impact of mucus layer and inlet air-temperatures on the particle deposition in a highly idealized mouth-throat model using LES

Presence of mucus layer and inlet air temperature variations can significantly affect the extent of particle transport and deposition in the mouth-throat airway for aerosol drug delivery applications. In addition, higher inlet air temperature can lead to thermal injuries as well. The main goal of the present paper is to investigate these effects in a highly idealized mouth-throat geometry in detail. Large eddy simulation was performed to accurately predict the air flow-fields and a Lagrangian particle tracking model has been employed to capture the particle deposition efficiencies and patterns. The effects of three different inlet air temperatures (15 °C, 26.7 °C and 45 °C) and three different particle sizes (3 μm, 5 μm and 6 μm) have been studied for inlet flow rates of 15 L/min and 30 L/min with and without mucus layer in the present investigation. Detailed velocity and temperature fields, as well as, particle deposition efficiencies and patterns were analyzed and it has been found out that (a) the particle deposition efficiencies varied significantly with changes in inlet air temperature and flow rates, particle diameters and in the presence of mucus layer, (b) the presence of recirculation zones and secondary vortices determined the rate of particle deposition at different inhalation flow rates and inlet air temperatures, and (c) the changes in temperature distribution near the mouth-throat wall in the presence of mucus layer have a dominant effect on particle deposition as compared to inertial deposition. The findings of the present work will provide useful information in understanding the heat transfer effects on particle transport and deposition for the design of pulmonary drug delivery devices under the influence of various environmental and human factors.

Numerical study of the impact of glottis properties on the airflow field in the human trachea using V-LES

The influences of the profiles and cross-sectional areas of glottal aperture on the upper respiratory airway are investigated using an idealized cast-based mouth-throat model and three dimensional computational fluid dynamics (CFD). The open source CFD code OpenFOAM is employed. The transient flows are modeled using the very-large eddy simulation with the Smagorinsky sub-grid scale (SGS) model. Five different shapes of glottis are considered, including circular glottis with 100 %, 75 % and 50 % cross-sectional area and elliptic glottis with 75 % and 50 % cross-sectional area. Both instantaneous and averaged flow fields are analyzed. It is found that the variations of glottis have great impacts on the properties of downstream flow fields such as the secondary flow, laryngeal jet, recirculation zone, turbulent kinetic energy, and vortex. Evident impacts are observed in the region within 6 tracheal diameters downstream of the glottis. The profile of the glottis has more impacts on the laryngeal shape, while the cross-sectional area has more impacts on velocity of the laryngeal jet and turbulent intensity. It is concluded that both the glottal areas and profiles are critical for an idealized geometrical mouth-throat model.

Evaluation of the stability of a spray-dried tuberculosis vaccine candidate designed for dry powder respiratory delivery

Particle engineering via spray drying was used to develop a dry powder presentation of an adjuvanted tuberculosis vaccine candidate. This presentation utilizing a trileucine-trehalose excipient system was designed to be both thermostable and suitable for respiratory delivery. The stability of the spray-dried vaccine powder was assessed over one year at various storage temperatures (-20, 5, 25, 40, 50 °C) in terms of powder stability, adjuvant stability, and antigen stability. A formulation without trileucine was included as a control. The results showed that the interior particle structure and exterior particle morphology of the powder was maintained for one year at 40 °C, while the control case exhibited a small extent of particle fusing under the same storage conditions. Moisture content was maintained, and powder solid state remained amorphous for all storage temperatures. Aerosol performance was assessed with a commercial dry powder inhaler in combination with a human mouth-throat model. The emitted dose and lung dose were maintained for all samples after one year at temperatures up to 40 °C. Nanoemulsion size and oil content of the adjuvant system were maintained after one year at temperatures up to 40 °C, and the agonist content was maintained after one year at temperatures up to 25 °C. The antigen was completely degraded in the control formulation at seven months of storage at 40 °C; by contrast, 45% of the antigen was still present in the trehalose-trileucine formulation after one year of storage at 50 °C. Comparatively, the antigen was completely degraded in a liquid sample of the vaccine candidate after only one month of storage at 37 °C. The spray-dried trehalose-trileucine vaccine powder clearly maintained its inhalable properties after one year’s storage at high temperatures and improved overall thermostability of the vaccine.

Can Pharmacokinetic Studies Assess the Pulmonary Fate of Dry Powder Inhaler Formulations of Fluticasone Propionate?

In the context of streamlining generic approval, this study assessed whether pharmacokinetics (PK) could elucidate the pulmonary fate of orally inhaled drug products (OIDPs). Three fluticasone propionate (FP) dry powder inhaler (DPI) formulations (A-4.5, B-3.8, and C-3.7), differing only in type and composition of lactose fines, exhibited median mass aerodynamic diameter (MMAD) of 4.5 μm (A-4.5), 3.8 μm (B-3.8), and 3.7 μm (C-3.7) and varied in dissolution rates (A-4.5 slower than B-3.8 and C-3.7). In vitro total lung dose (TLDin vitro) was determined as the average dose passing through three anatomical mouth-throat (MT) models and yielded dose normalization factors (DNF) for each DPI formulation X (DNFx = TLDin vitro,x/TLDin vitro,A-4.5). The DNF was 1.00 for A-4.5, 1.32 for B-3.8, and 1.21 for C-3.7. Systemic PK after inhalation of 500 μg FP was assessed in a randomized, double-blind, four-way crossover study in 24 healthy volunteers. Peak concentrations (Cmax) of A-4.5 relative to those of B-3.8 or C-3.7 lacked bioequivalence without or with dose normalization. The area under the curve (AUC0-Inf) was bio-IN-equivalent before dose normalization and bioequivalent after dose normalization. Thus, PK could detect differences in pulmonary available dose (AUC0-Inf) and residence time (dose-normalized Cmax). The differences in dose-normalized Cmax could not be explained by differences in in vitro dissolution. This might suggest that Cmax differences may indicate differences in regional lung deposition. Overall this study supports the use of PK studies to provide relevant information on the pulmonary performance characteristics (i.e., available dose, residence time, and regional lung deposition).

LES study of the respiratory airflow field in a whole-lung airway model considering steady respiration

It is critical to understand the airflow structures in the respiratory system toward increasing the drug delivery efficiency via inhalation. A whole-lung airway model is created by connecting a three-dimensional cast-based mouth–throat model and a one-dimensional conduit describing the other lung airways according to the literature. Constant displacement of the bottom surface in the geometrical model is used to simulate the respiratory process. Large eddy simulation with the dynamic structure sub-grid scale model is used to model the turbulent flow via a commercial computational fluid dynamics software, ConvergeTM. The innovative findings are as follows: (1) shear layer as well as vortical flow is observed in the lower airway at the inspiration phase; (2) the main airflow structures in the upper airway of this model are close to the case using the mouth–throat model; (3) the airflow structures, in particular the reversed laryngeal jet, are highly unsteady during the expiration phase. It is shown that this whole-lung airway model is suitable to analyze the airflow field in the upper airway but not in the lower airway, although it has been used a lot by a few researchers. More investigations should be carried out to study the dynamics of airflow structures during the expiration phase toward understanding airflow properties of human respiratory process.

Investigation of airflow field in the upper airway under unsteady respiration pattern using large eddy simulation method

In this paper, the airflow field in the upper airway under unsteady respiration process is predicted using large eddy simulation. The geometrical model is created by combining a popular cast-based mouth–throat model with tracheo-bronchial airways modeled with a trumpet-shaped conduit. The respiration process is simulated by sinusoidal displacing the bottom surface of the geometrical model. Large eddy simulation with dynamic sub-grid scale model is adopted for modeling the turbulent flow via a commercial CFD software, Converge. This study has found that (1) the secondary vortices in the mouth cavity are much more complex considering the lung expansion than setting the quasi-steady inspiration flow at the mouth-inlet; (2) the properties of secondary vortices in the trachea are not evidently different at the same Reynolds number at the accelerating and decelerating inspiration phases; (3) the reversed pharynx jet as well as recirculation zone is much unsteadier at the accelerating expiration phase than decelerating expiration phase for the same Reynolds number. We conclude that the properties of airflow structures are highly impacted by the respiration pattern and more investigations should be conducted, particularly, on the airflow structures during expiration phase for further understanding the properties of flow field.

Evaluation of Bio-relevant Mouth-Throat Models for Characterization of Metered Dose Inhalers.

For inhalation drug characterization, the traditionally used USP induction port provides limited in vivo predictive capability because it does not adequately mimic airway geometry. In this study, various bio-relevant mouth-throat (MT) models, including Alberta Idealized Throat (AIT), and 3D printed large/medium/small-sized VCU (Virginia Commonwealth University) models were evaluated using two metered dose inhaler (MDI) drug products: a solution MDI containing beclomethasone dipropionate (BDP-MDI) and a suspension MDI containing fluticasone propionate (FP-MDI). For BDP-MDI, use of VCU large and small MT models resulted in a significantly higher MT deposition and lower fine particle fraction (FPF) compared with the other MT models. In the case of FP-MDI, the three VCU models resulted in higher MT deposition and lower FPF compared with the USP induction port and AIT. Overall, the in vitro testing results for the suspension MDI were more sensitive to geometric differences of the MT models than those for the solution MDI. Our results suggest that in vitro characterization of MDI products can be influenced by many factors, including the type of formulation, the MT geometry, shape, internal space volume, and the material used to make the MT models.