A 3D printed human upper respiratory tract model for particulate deposition profiling

Lim, Seng Han; Park, Sol; Lee, Chun Chuan; Ho, Peiying; Kwok, Philip Chi Lip; Kang, Lifeng

doi:10.1016/j.ijpharm.2021.120307

Cited by 22 publications

(7 citation statements)

References 59 publications

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“…It compares the effect of aerosol bursts and momentum on drug deposition. About %55 of the particles injected from the conventional pMDI nozzle deposited in the MT, and the remaining particles passed through the trachea, in agreement with in vitro results (Biswas et al 2017;Kaviratna et al 2019;Lim et al 2021) and CFD modelling studies (Kleinstreuer et al 2007; Walenga and Longest 2016) with similar MT geometries. Less than %2 and %3 deposited in the mouth and trachea region, respectively.…”

Section: Regional Depositionsupporting

confidence: 81%

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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Section: Regional Depositionsupporting

confidence: 81%

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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“…For lung deposition, cascade impactors are known to have at best modest correlation with in vivo lung deposition data due to differences in “mouth-throat” geometry and inhalation profiles [ 132 ]. IVIVC could be improved by employing realistic “mouth-throats” connected to cascade impactors or 3D-printed lung models and simulated breathing profiles [ 117 , 133 ], yet the selection of suitable anatomical “mouth-throats” and representative inhalation profiles remains to be controversial. Alternatively, in silico modeling by computational fluid dynamics (CFD) is a trendy strategy in predicting in vivo deposition, though they are more technically demanding compared to in vitro methods [ 134 ].…”

Section: Challenges and Knowledge Gaps For Clinical Translationmentioning

confidence: 99%

Inhalable Nanoparticle-based Dry Powder Formulations for Respiratory Diseases: Challenges and Strategies for Translational Research

et al. 2023

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The emergence of novel respiratory infections (e.g., COVID-19) and expeditious development of nanoparticle-based COVID-19 vaccines have recently reignited considerable interest in designing inhalable nanoparticle-based drug delivery systems as next-generation respiratory therapeutics. Among various available devices in aerosol delivery, dry powder inhalers (DPIs) are preferable for delivery of nanoparticles due to their simplicity of use, high portability, and superior long-term stability. Despite research efforts devoted to developing inhaled nanoparticle-based DPI formulations, no such formulations have been approved to date, implying a research gap between bench and bedside. This review aims to address this gap by highlighting important yet often overlooked issues during pre-clinical development. We start with an overview and update on formulation and particle engineering strategies for fabricating inhalable nanoparticle-based dry powder formulations. An important but neglected aspect in in vitro characterization methodologies for linking the powder performance with their bio-fate is then discussed. Finally, the major challenges and strategies in their clinical translation are highlighted. We anticipate that focused research onto the existing knowledge gaps presented in this review would accelerate clinical applications of inhalable nanoparticle-based dry powders from a far-fetched fantasy to a reality. Graphical Abstract

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“…we observed whether the solenoid pressed the driver, the upper computer software could adequately receive the monitoring results in real time, and whether the receiving function worked normally; the test results were analyzed and are summarized in Table 6. The interval time was calculated using Equation (14). ∆t = STA × 65535 + VAL + t e (14) where STA denotes the number of overflows, VAL denotes the current channel value of the timer, and t e denotes the driving time of the push-pull solenoid, which was set to approximately 9 ms for this study.…”

Section: Inspiration-press Synchronization Testmentioning

confidence: 99%

“…The interval time was calculated using Equation (14). ∆t = STA × 65535 + VAL + t e (14) where STA denotes the number of overflows, VAL denotes the current channel value of the timer, and t e denotes the driving time of the push-pull solenoid, which was set to approximately 9 ms for this study.…”

Section: Inspiration-press Synchronization Testmentioning

confidence: 99%

“…One such canister is the fog storage container, which is an extension of the drive embouchure; that is, a large-volume canister is attached to the spray outlet, which enables temporary storage of drug particles and mitigates the problems of high oral and throat drug deposition rates resulting from excessive aerosol velocities. Although such mist storage containers can effectively reduce the rate of oral and throat deposition, significant amounts of drugs are deposited in the container, which may not improve the rate of drug deposition in the lungs [14]. In contrast to the storage mist canisters, the concept of the inhaler-driven aerosol design achieves the function of synchronizing patient inhalation and aerosol compression via a specially designed structure or device, thereby reducing the rate of drug deposition in the oropharynx [15].…”

Section: Introductionmentioning

confidence: 99%

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Development of a Smart Metered-Dose Inhaler for Asthma Based on Computational Fluid Dynamics

Zhang,

Wei

2023

Symmetry

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Asthma is a common respiratory disease with symptoms such as repeated wheezing, shortness of breath, and coughing. However, currently, asthma cannot be cured but only controlled or relieved using medication. The metered-dose inhaler (MDI) is known to lead to high deposition fractions of drug particles in the mouth and throat, resulting in inadequate drug efficacy. Therefore, herein, the factors influencing the deposition fraction of asthma drugs in the mouth and throat regions were explored by computational fluid dynamics and a smart MDI for asthma was designed. The smart MDI was designed based on the obtained simulation results, which demonstrated that the deposition fraction gradually increased from 55.78% to 65.75% with an increase in the peak inspiratory flow rate at an angle of incidence of 0°. The deposition fraction first decreased and then increased as the angle of incidence increased at a constant peak inspiratory flow rate. The deposition fraction increased as the inspiration–press interval time increased at a constant angle of incidence and peak inspiratory flow rate. Meanwhile, performance analysis of the designed smart MDI indicated that the inhaler could effectively reduce the deposition fraction of drugs in the mouth and throat regions by 17% on average.

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A 3D printed human upper respiratory tract model for particulate deposition profiling

Cited by 22 publications

References 59 publications

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

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

Inhalable Nanoparticle-based Dry Powder Formulations for Respiratory Diseases: Challenges and Strategies for Translational Research

Development of a Smart Metered-Dose Inhaler for Asthma Based on Computational Fluid Dynamics

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