Combined in Vitro-in Silico Approach to Predict Deposition and Pharmacokinetics of Budesonide Dry Powder Inhalers

Ruzycki, Conor A.; Murphy, Brynn; Nathoo, Hafeez; Finlay, Warren H.

doi:10.1007/s11095-020-02924-7

Cited by 9 publications

(3 citation statements)

References 70 publications

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“…FIGURE 5 | Comparison of amounts predicted to deposit in the tracheobronchial (TB) and alveolar regions using NGI impactor data combined with in silico regional deposition modeling (Javaheri et al, 2013) aerosols Ruzycki et al (2020) found the transverse position with the Alberta Idealized Throat improved agreement with in vivo extrathoracic deposition data.…”

Section: Benchtop Measurement Of Regional Deposition With Inhalersmentioning

confidence: 94%

“…By a similar argument, in some cases it may also be useful to discriminate between the tracheobronchial versus alveolar components of the total lung dose. Until recently, the simplest in vitro procedure for separating the lung dose into its morphological components was to measure the aerosol size distribution, typically using multistage cascade impaction, and input this into a computer model that provides estimates of regional lung deposition for the given particle size distribution and chosen inhalation pattern (e.g., Ruzycki et al, 2020;Miller et al, 2021). This labor-intensive task is complicated by the need for a mixing inlet when using realistic breathing patterns.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Estimation of Tracheobronchial and Alveolar Doses Using Filters

Finlay

Farina²,

Tavernini

2022

Front. Drug. Deliv.

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To date, in vitro estimation of doses delivered by an inhaler to the different major regions of the lung has required combining particle size measurements of the inhaled aerosol with in silico deposition models. Such a two step process is labor and time intensive. Here, we describe instead the development of an apparatus that allows direct estimation of regional lung deposition by measurement of doses collected on purpose-built metal grid filters that mimic tracheobronchial deposition efficiency. Placing these filters downstream of the Alberta Idealized Throat and upstream of a final filter allows collection of doses depositing in the extrathoracic, tracheobronchial and alveolar regions. Artificial electrostatic deposition on the metal tracheobronchial filters is prevented by a custom inline electrostatic neutralizer. We use the resulting apparatus to estimate regional deposition with a variety of dry powder inhalers during realistic, time-varying inhalation maneuvers and three pMDIs with a constant flow rate of 30 l/min. These results are compared to those obtained with the traditional two step approach that combines cascade impaction with a regional deposition model. Good agreement is found between the two approaches, indicating that the present direct method may be an efficient, time-saving alternative method for in vitro estimation of regional lung doses.

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Section: Benchtop Measurement Of Regional Deposition With Inhalersmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

In Vitro Estimation of Tracheobronchial and Alveolar Doses Using Filters

Finlay

Farina²,

Tavernini

2022

Front. Drug. Deliv.

Self Cite

View full text Add to dashboard Cite

show abstract

“…If differences in TLD are to be relied upon, it is preferred that these measurements come from in vivo clinical studies (i.e., imaging or charcoal block pharmacokinetics methods). Alternatively anatomical throat models (e.g., the Alberta Idealized Throat, AIT), particularly when using realistic inspiratory flow profiles, have demonstrated good in vitro/in vivo correlations (Zhang et al, 2007;Byron et al, 2010;Delvadia et al, 2012;Olsson et al, 2013;Finlay and Martin, 2015;Weers et al, 2015;Ruzycki et al, 2019;Newman and Chan, 2020;Ruzycki et al, 2020). The last choice for estimates of TLD should be cascade impactors.…”

Section: Minimum Threshold Energymentioning

confidence: 99%