Drug distribution transients in solution and suspension-based pressurised metered dose inhaler sprays

Duke, Daniel J.; Scott, Harry N.; Kusangaya, Anesu J.; Kastengren, Alan L.; Matusik, Katarzyna E.; Young, Paul M.; Lewis, David; Honnery, Damon

doi:10.1016/j.ijpharm.2019.05.067

Cited by 11 publications

(10 citation statements)

References 28 publications

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“…In the mouththroat airway, the main force on micron particles is the drag force and the gravitational force is negligible [46]. Additionally, in the upper and large airways as well, the gravitational force on micron particles is negligible in comparison with the particle drag force [24]. Particle sizes in a polydisperse aerosol can range over two or more orders of magnitude.…”

Section: Governing Equationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Duke et al [24] demonstrated in vitro that approximately 20% of the total cumulative dose was delivered to the lung in the first 0.1 s of the spray. They noticed a rapid drop in drug mass fraction in the upper airway due to the drug deposition in that area [24]. They concluded that the leading particles at the edge of the aerosol plume encounter a drag force against still air and thus experience less particle/particle interactions in comparison with the particles that follow [24].…”

Section: Introductionmentioning

confidence: 99%

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A CFD Investigation on the Aerosol Drug Delivery in the Mouth–Throat Airway Using a Pressurized Metered-Dose Inhaler Device

et al. 2022

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Inhalation therapy involving a pressurized metered-dose inhaler (pMDI) is one of the most commonly used and effective treatment methods for patients with asthma. The purpose of this study was to develop a computational fluid dynamics (CFD) model to characterize aerosol flow issued from a pMDI into a simulated mouth–throat geometry. The effects of air flow rate and cone angle were analyzed in detail. The behaviour of the multiphase flow initiated at the inhaler actuation nozzle and extended through the mouth–throat airway was simulated based on the Eulerian-Lagrangian discrete phase model, with the k-ω model applied for turbulency. We validated our model against published experimental measurements and cover the hydrodynamic aspect of the study. The recirculation we observed at the 90° bend inside the mouth–throat airway resulted in the selective retention of larger diameter particles, and the fluid flow patterns were correlated with drug deposition behaviour. Enhancing air flow rates up to three times reduced the aerodynamic particle diameters to 20%. We also observed that, as cone angle increased, mouth deposition increased; an 8° cone angle was the best angle for the lowest mouth–throat deposition.

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Section: Governing Equationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A CFD Investigation on the Aerosol Drug Delivery in the Mouth–Throat Airway Using a Pressurized Metered-Dose Inhaler Device

et al. 2022

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“…However, even with these excellent features of pMDIs, only 5-30% of the medication reaches the treatment area of the lung; in other words, the delivered drugs tend to deposit in the mouth-throat (MT) region before reaching the target region (McKiernan 2019). An accurate understanding of the initial plume formation and expansion would help to improve the efficiency of the device; however physical and behavioural characterization of the pMDI is complex, due to the entirely transient, turbulent, threedimensional, and multiphase nature of the spray (Duke et al 2019;Ogrodnik et al 2016).…”

Section: Introductionmentioning

confidence: 99%

The Impact of Actuator Nozzle and Surroundings Condition on Drug Delivery using Pressurized-Metered Dose Inhalers

Jahed

Koziński

Pakzad

2023

Preprint

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The most commonly used method to deliver aerosolized drugs to the lung is with pressurized metered-dose inhalers (pMDIs). The spray actuator is a critical component of a pMDI, since it controls the atomization process by forming aerosol plumes and determining droplet size distribution. Through computational fluid dynamics (CFD) simulations, this study investigated the effect of two different nozzle types (single conventional and twin nozzles) on drug deposition in the mouth-throat (MT) region. We also studied the behavior of aerosol plumes in both an open-air environment and the MT geometry. Our study revealed that spray aerosol generated in an unconfined, open-air environment with no airflow behaves distinctly from spray introduced into the MT geometry in the presence of airflow. In addition, the actuator structure significantly impacts the device's efficacy. In the real MT airway, we found that the twin nozzle increases drug deposition in the MT region and its higher aerosol velocity negatively affects its efficiency.

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“…Visualization of MDI actuation and aerosol formation has been attempted by using high-speed camera, laser diffraction, Schlieren optical imaging, and phase-contrast X-ray imaging [31][32][33][34][35][36][37]. With a laser and high-speed camera, Smyth et al observed asymmetrical and ellipsoid spray cross-sections in the vertical direction [38].…”

Section: Introductionmentioning

confidence: 99%

Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model

Talaat

2022

Pharmaceuticals

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Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in actuation–inhalation coordination, and the complex lung networks. The objective of this study was to develop/validate a computational MDI-releasing-delivery model and to evaluate the device actuation effects on the dose distribution with the newly developed model. An integrated MDI–mouth–lung (G9) geometry was developed. An albuterol MDI with the chlorofluorocarbon propellant was simulated with polydisperse aerosol size distribution measured by laser light scatter and aerosol discharge velocity derived from measurements taken while using a phase Doppler anemometry. The highly transient, multiscale airflow and droplet dynamics were simulated by using large eddy simulation (LES) and Lagrangian tracking with sufficiently fine computation mesh. A high-speed camera imaging of the MDI plume formation was conducted and compared with LES predictions. The aerosol discharge velocity at the MDI orifice was reversely determined to be 40 m/s based on the phase Doppler anemometry (PDA) measurements at two different locations from the mouthpiece. The LES-predicted instantaneous vortex structures and corresponding spray clouds resembled each other. There are three phases of the MDI plume evolution (discharging, dispersion, and dispensing), each with distinct features regardless of the actuation time. Good agreement was achieved between the predicted and measured doses in both the device, mouth–throat, and lung. Concerning the device–patient coordination, delayed MDI actuation increased drug deposition in the mouth and reduced drug delivery to the lung. Firing MDI before inhalation was found to increase drug loss in the device; however, it also reduced mouth–throat loss and increased lung doses in both the central and peripheral regions.

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Drug distribution transients in solution and suspension-based pressurised metered dose inhaler sprays

Cited by 11 publications

References 28 publications

A CFD Investigation on the Aerosol Drug Delivery in the Mouth–Throat Airway Using a Pressurized Metered-Dose Inhaler Device

A CFD Investigation on the Aerosol Drug Delivery in the Mouth–Throat Airway Using a Pressurized Metered-Dose Inhaler Device

The Impact of Actuator Nozzle and Surroundings Condition on Drug Delivery using Pressurized-Metered Dose Inhalers

Effect of MDI Actuation Timing on Inhalation Dosimetry in a Human Respiratory Tract Model

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