Lung Deposition Using the Respimat<sup>®</sup> Soft Mist™ Inhaler Mono and Fixed-Dose Combination Therapies: An <i>In Vitro</i>/<i>In Silico</i> Analysis
Bibliographic record
Abstract
Tiotropium and olodaterol are mainstay treatments for chronic obstructive pulmonary disease (COPD) and yield important clinical improvements, especially when used in fixed-dose combination. Whilst previous studies have shown consistent delivery of tiotropium to the lungs with the Respimat® inhaler, no such study has been carried out for olodaterol or the components of their fixed-dose combination (TIO/OLO). Combining in vitro and in silico models, we measured the amount of drug retained in the mouth–throat area, entering the trachea and reaching the lung periphery. We applied a hybrid deposition model that considered the experimentally determined output of an Alberta throat model (in vitro – dose to lung) combined with a computational fluid dynamic model of the lungs (in silico). Regardless of the COPD breathing pattern, ≥50% of the nominal dose of either tiotropium, olodaterol, or TIO and OLO in the fixed-dose combination reached the lung. Of the dose reaching the lungs, greater than 50% is deposited in the lung periphery (from generation 8 onwards). Our study demonstrated that aerosol delivery via the Respimat inhaler achieved high deposition deep into the lung periphery with all formulations evaluated.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".