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Pressurized metered dose inhalers (pMDI) are one of the most common devices to deliver therapeutic treatment to patients with asthma or COPD. The atomization mechanism responsible for droplet production is poorly understood because of the short length and timescales involved, making experimental investigations to characterize fluid flow structures and spray formation processes difficult. This article reports the findings of new high-speed and high-resolution imaging and temperature measurements seeking to improve the fundamental understanding of the atomization mechanism of the pMDI. An annular flow regime of gaseous core in liquid annulus was observed in the orifice. Shock diamonds within the flow, viewed via Schlieren imaging, confirmed experimentally for the first time the choked nature of the orifice exit flow. Propellant formulation flow in the orifice was found to be superheated to a degree that significant flashing and evaporation at the orifice exit is likely to take place. This information points to a hybrid mechanism of predominantly aerodynamic atomization with significant liquid flashing upon exit from the orifice producing a near instantaneous formation of respirable droplets. Large irrespirable droplets are produced by two mechanisms; breakup of liquid slugs ejected from the orifice, due to unsteady transient fluid structures in the actuator sump and stripping of ligaments from a liquid pool around the orifice exit, which subsequently break up into large droplets in the periphery of the plume. This new understanding will aid development of next generation, high efficiency pMDIs, particularly those employing low global warming potential propellants such as HFA152a or HFO1234ze(E). Copyright © 2022 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

We describe a computational model that captures the physics of the unsteady air-flow startup that accompanies the testing of dry-powder inhalers (DPI) with cascade impactors (CIs) specifically when following methods described in the pharmacopeial compendia. This transient has been measured in a multi-organization study for a wide range of conditions and reported in a companion article. The DPI test system is simulated as a series of flow resistances, starting with the inhaler itself, including each stage of the CI, and finishing with the prescribed flow control valve, wherein the flow is held at sonic velocity. The resulting non-dimensional equations indicate the relative importance of the several flow resistances. The model agrees well with the available experimental data for the Next Generation Impactor (NGI™) and qualitatively with the available data from a variety of the configurations of the Andersen 8-stage cascade impactor (ACI), including the typical 4-kPa pressure drop across an entry fixed orifice mimicking surrogate low-, medium- and high-resistance DPIs. The model indicates that the startup times for the NGI and for the ACI are very reasonably estimated by a simple "reference time," given in Equation (26) and, for an inlet flow rate of 60 L/min, having a value of 277 ms and 113 ms for the NGI and ACI (60-L/min configuration), respectively. The model also enables a baseline, universal design curve for the flow rise-time performance of testing DPIs with the NGI (Figures 9a and b), because this impactor requires no change of components for any inlet flow rate. Copyright © 2020 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

We report a cross-industry study characterizing flow rate-time profiles of equipment used for testing dry-powder inhalers (DPIs). Nine organizations used the same thermal mass flow sensor to record flow rate-time profiles at the inlet of individual participant compendial DPI test systems including either sample collection tubes (SCT), the Andersen 8-stage non-viable impactor (ACI) or the Next Generation Impactor (NGI™) with and without pre-separator (PS). The plan included some tests with a surrogate DPI consisting of one of three inlet orifices chosen to generate a 4-kPa pressure drop at each of the target final flow rates of 30, 60, and 90 l.min−1, simulating the pressure drop typical of high-, medium-, and low-resistance DPIs. When a particular surrogate DPI was present at the inlet, rise times to 90% of these target flow rates (t90) were shortest at the highest target flow rate, and decreased linearly with decreasing apparatus internal volume, following the order: NGI-PS > NGI > ACI-PS > ACI > SCT. A flow acceleration parameter was also evaluated, expressed as the slope between the rise times when the flow rate attained 20% and 80% of each final steady flow rate (slopet20/80). Flow acceleration was smallest at the lowest target flow rate, decreasing exponentially with increasing internal volume. Measurements were also made without the surrogate DPI, providing a reference condition with no resistance at the inlet to the apparatus. These flow rate-rise time profiles will be useful for those involved in evaluating equipment for characterizing DPIs and in understanding the behavior of these inhalers in development or commercial production. Copyright © 2020 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

This article reports the extension to binary propellant/excipient mixtures of the multiphase model of transient internal flow and atomization in pressurized metered dose inhalers (pMDIs) of Gavtash and colleagues for propellant-only flows. The work considers different accounts of the effect of less volatile ethanol on the saturated vapor pressure (SVP), viscosity and surface tension of HFA-based pMDI formulations. Representation of the SVP of HFA/ethanol mixtures by Raoult's law is compared with the empirical model developed by Gavtash and colleagues as well as different theoretical mixing rules for surface tension and viscosity. For initial ethanol contents ranging from 0 to 20% by mass, the temperature, pressure and spray velocity were predicted to be almost independent of ethanol concentration when using the empirical SVP model of Gavtash and colleagues. The predicted aerosol droplet size increases with increasing concentration of ethanol. These model predictions compare favorably with phase Doppler anemometry (PDA) measurements of pMDI sprays. Exploration of model predictions with different mixing rules suggest that variations of the dynamic viscosity could result in 0.7 µm droplet size change, and different surface tension models yield around 1.5 µm droplet size change. The findings of this work challenge the view that the increase of droplet size is caused by the low volatility of excipients such as ethanol. Instead, attention is focused on composition-dependent viscosity and surface tension as potential controlling parameters with significant effect on the droplet size of HFA/ethanol sprays. Copyright © 2018 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

Pressurized metered dose inhalers (pMDI) produce large numbers of droplets with smaller sizes than 5 μm to treat asthma and other pulmonary diseases. The mechanism responsible for droplet generation from bulk propellant liquid is poorly understood, mainly because the small length scales and short time scales make it difficult to characterize transient spray formation events. This article describes the development and findings of a numerical atomization model to predict droplet size of pharmaceutical propellants from first principles. In this model, the velocity difference between propellant vapor and liquid phase inside spray orifice leads to formation of wave-like instabilities on the liquid surface. Two variants of the aerodynamic atomization model are presented based on assumed liquid precursor geometry: (1) cylindrical jet-shaped liquid ligaments surrounded by vapor annulus; (2) annular liquid film with vapor flow in the core. The growth of instabilities on the liquid precursor surfaces and the size of the subsequently formed droplets are predicted by numerical solutions of dispersion equations. The droplet size predictions were compared with phase doppler anemometry (PDA) data and the predictions were in good agreement with the number mean diameterD10, which is representative of the respirable droplets. The temporal behavior of droplet size production was captured consistently well during the period of the first 95% of the propellant mass emission. The outcome of our modeling activities also suggests that, in addition to saturated vapor pressure of the propellant, its viscosity and surface tension are also key properties that govern pMDI droplet size. © 2017 American Association for Aerosol Research [ABSTRACT FROM PUBLISHER]

Despite the popularity of the pMDI as an asthma remedy, the mechanism leading to spray generation is elusive, mainly due to small length scales and short time scale, causing experimental difficulties to obtain flow information. This mechanism involves transient development of two-phase flashing propellant flow inside pMDI actuator as well as transfer of heat, mass, and momentum between the liquid and vapor phase. Variations in the rate of such interphase phenomena dictate the two-phase mass flow rate emission, which itself determines spray velocity and droplet size. In this work, we compare the performance of existing two-phase flow models to predict the flow conditions and the rate of propellant flow through a pMDI actuator: the homogenous equilibrium model (HEM), the slip equilibrium model (SEM), and the homogenous frozen model (HFM). The velocity prediction of the HFM was found to be in good agreement with phase Doppler anemometry (PDA) data indicating the metastable nature of the emitted propellant spray. This work also considers Clark's correlation for the aerosol droplet size based on the results of the flow model. The results of the correlation were compared with PDA droplet size measurements. Clark's correlation was found to be effective in predictions of the temporal droplet size variations. However, the value of an empirical constant had to be tuned to fix the droplet size for a given combination of formulation, device, and to a lesser extent also the distance from the spray orifice where predictions are compared with PDA data. This highlights the need to develop first principle atomization models without the need for case-by-case adjustment. © 2017 American Association for Aerosol Research [ABSTRACT FROM PUBLISHER]

The discrete transfer method (DTM) is a widely used algorithm for the computation of radiative heat transfer in enclosures. The truncation error in the heat flux integral associated with the method is the difference between the actual heat flux and its DTM approximation. Estimates were presented by Versteeg et al. [1, 2] of the error associated with the discretization of the hemisphere around irradiated points in enclosures filled with transparent and nonscattering participating media. In this article we quantify the errors due to the spatial discretisation of the enclosure surface and medium conditions. We have studied radiation problems in enclosures with nonhomogeneous absorbing/emitting media with nonuniform surface intensity based on Hsu and Farmer's benchmark case E1 [3]. Our error estimates are found to be in excellent agreement with the actual DTM errors and have been used successfully to predict the convergence rates of the DTM as the control-volume mesh is refined. [ABSTRACT FROM AUTHOR]

A method is presented to quantify truncation errors in the discrete transfer method due to discretization of the heat flux integral (hemisphere discretization error) and enclosure boundaries (surface discretization error) for radiation problems involving transparent media. The hemisphere discretization error is generally the larger of the two. Its rate of decay with increasing ray number NR depends strongly on the degree of continuity of the intensity field. For continuous intensity distributions the rate of error decay is proportional to 1/NR, but for piecewise-continuous fields the rate is proportional to 1/square root NR. The surface discretization error causes a small systematic error in the average surface heat flux in a finite-volume CFD/heat transfer calculations. The success of our theory has paved the way to economical error estimation in practically relevant cases. [ABSTRACT FROM AUTHOR]

The truncation error in the heat flux integral associated with the discrete transfer method (DTM) is the difference between the actual heat flux and its approximation. Estimates of this error in radiative heat transfer problems in enclosures filled with a transparent medium were presented in a companion article [1]. Here we extend the methodology to cases in volving participating media. We give expressions for the errors associated with the discretization of the heat flux integral for enclosures where the surface intensity and medium source function are known exactly and represented as piecewise constant. Excellent agreement between theoretical and computed errors was found for three illustrative test cases. The theory was also applied to one of the cases of the well-known Hsu and Farmer (1995) benchmark [9]. A good match was obtained between the error limits of the Monte Carlo and DTM solutions. [ABSTRACT FROM AUTHOR]