Development of a stochastic individual path (SIP) model for predicting the tracheobronchial deposition of pharmaceutical aerosols: Effects of transient inhalation and sampling the airways

Tian, Geng; Longest, P. Worth; Su, Guoguang; Walenga, Ross; Hindle, Michael

doi:10.1016/j.jaerosci.2011.07.005

Cited by 96 publications

(158 citation statements)

References 76 publications

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“…(26) A sufficient number of stochastically generated pathways are simulated until deposition results converge to an ensemble average. (16) This approach is reported to reduce the required time to simulate the full TB region by a factor of 3 · 10 5 with only an estimated minor loss in accuracy. (16) Recently, we extended the SIP modeling approach to include the entire lung by developing correlations of aerosol deposition in representative models of complete acinar regions using inhalation profiles consistent with pharmaceutical inhalers.…”

Section: Introductionmentioning

confidence: 93%

“…(16) This approach is reported to reduce the required time to simulate the full TB region by a factor of 3 · 10 5 with only an estimated minor loss in accuracy. (16) Recently, we extended the SIP modeling approach to include the entire lung by developing correlations of aerosol deposition in representative models of complete acinar regions using inhalation profiles consistent with pharmaceutical inhalers. (53) Combining the SIP modeling approach with the new CFD predictions of alveolar deposition provides a CFD-based technique to simulate pharmaceutical aerosol delivery throughout the airways beginning with the site of aerosol formation.…”

Section: Introductionmentioning

confidence: 93%

“…(15) The use of CFD whole-lung models to predict pharmaceutical aerosol deposition throughout the lungs is a new development, (1,(16)(17)(18) and validations with multiple in vivo studies are currently needed.…”

Section: Introductionmentioning

confidence: 99%

“…(1,16,17) A primary advantage of this approach is the flexibility to directly include new aspects of aerosol physics for developing new delivery strategies and inhalers. A disadvantage is that it remains difficult to implement due to the complexity of the underlying physics.…”

Section: Introductionmentioning

confidence: 99%

“…To predict deposition throughout the tracheobronchial airways, our group has developed the stochastic individual pathway (SIP) modeling approach. (1,16,17) In this method, individual continuous pathways beyond the third bifurcation (B3) are generated extending into each lobe of the lung through the terminal bronchioles (B15). Along each pathway, one daughter branch of each bifurcation is continued and one is not, which is similar to the 1D whole lung Monte Carlo modeling technique of Koblinger and Hofmann.…”

Section: Introductionmentioning

confidence: 99%

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Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

Longest

Tian

Khajeh-Hosseini-Dalasm

et al. 2016

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Background: The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition. Methods: The Novolizer DPI with a budesonide formulation was selected based on the availability of 2D gamma scintigraphy data in humans for three different well-defined inhalation waveforms. Initial in vitro cascade impaction experiments were conducted at multiple constant (square-wave) particle sizing flow rates to characterize PSDs. The whole-airway CFD modeling approach implemented the experimentally determined PSDs at the point of aerosol formation in the inhaler. Complete characteristic airway geometries for an adult were evaluated through the lobar bronchi, followed by stochastic individual pathway (SIP) approximations through the tracheobronchial region and new acinar moving wall models of the alveolar region. Results: It was determined that the PSD used for each inhalation waveform should be based on a constant particle sizing flow rate equal to the average of the inhalation waveform's peak inspiratory flow rate (PIFR) and mean flow rate [i.e., AVG(PIFR, Mean)]. Using this technique, agreement with the in vivo data was acceptable with <15% relative differences averaged across the three regions considered for all inhalation waveforms. Defining a peripheral to central deposition ratio (P/C) based on alveolar and tracheobronchial compartments, respectively, large flow-rate-dependent differences were observed, which were not evident in the original 2D in vivo data. Conclusions: The agreement between the CFD predictions and in vivo data was dependent on accurate initial estimates of the PSD, emphasizing the need for a combination in vitro-in silico approach. Furthermore, use of the AVG(PIFR, Mean) value was identified as a potentially useful method for characterizing a DPI aerosol at a constant flow rate.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

Longest

Tian

Khajeh-Hosseini-Dalasm

et al. 2016

Journal of Aerosol Medicine and Pulmonary Drug Delivery

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Design of a numerical model of lung by means of a special boundary condition in the truncated branches

Tena

Pastor

Álvarez

et al. 2016

Numer Methods Biomed Eng

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Prediction of Transport and Deposition of Porous Particles in the Respiratory System Using Eulerian–Lagrangian Approach

Eshaghi,

Khaleghi,

Maddahian

2024

Numer Methods Biomed Eng

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Deep lung delivery is crucial for respiratory disease treatment. Although nano and submicron particles exhibited a good deposition efficiency in deep regions of the lung, powder nonuniformity and particle agglomeration reduce their efficiency. Inhalation of porous particles (PPs) can overcome the mentioned challenges due to their larger size and low‐density. The present study numerically investigates the deposition and penetration efficiency of orally inhaled PPs. A revised drag coefficient was implemented for PP transport. A realistic mouth–throat to the fifth generation of the lung was reconstructed from CT‐scan images. A dilute suspension of uniformly distributed particles was considered at three inhalation flow rates (15, 30, and 45 L/min). Governing equations of the flow field and particle transport are solved using an Eulerian–Lagrangian approach. The results demonstrate that inhaling PPs significantly reduces the total and regional deposition of particles. There was also a critical porosity value under moderate and high inhalation flow rates for large PPs. Below this critical value, PP deposition efficiency substantially decreases. Additionally, it was also found that under low inhalation flow rates, the impact of porosity value is negligible. Almost 95% of the PPs penetrate the lower branches. These findings provide particle engineers and pharmaceutics with profound insight into developing novel inhalation techniques and drug delivery methods for deep lung delivery.

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Development of a stochastic individual path (SIP) model for predicting the tracheobronchial deposition of pharmaceutical aerosols: Effects of transient inhalation and sampling the airways

Cited by 96 publications

References 76 publications

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

Design of a numerical model of lung by means of a special boundary condition in the truncated branches

Prediction of Transport and Deposition of Porous Particles in the Respiratory System Using Eulerian–Lagrangian Approach

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