The Influence of Pressurized Metered Dose Inhaler Actuator Orifice Diameter on Regional Extrathoracic Deposition of Inhaled Epinephrine
Bibliographic record
Abstract
Background: Extrathoracic deposition is a large source of in vivo variability in dosing for pressurized metered dose inhaler (pMDI) aerosols. A majority of previous studies have focused on only total extrathoracic deposition for pMDIs. The present work evaluates regional deposition within the extrathoracic region to better understand the impact of actuator orifice diameter and inhalation flow rate on extrathoracic deposition of a suspension pMDI formulation of epinephrine. Methods: Regional deposition of a commercially available HFA (hydrofluoroalkane) suspension pMDI formulation of epinephrine was evaluated using plastic and metal versions of the newly developed sectioned Alberta Idealized Throat (s-AIT), divided into analogs of the oral cavity, the pharynx/larynx, and the upper trachea. Influences of actuator orifice diameter and inhaler insertion angle on regional extrathoracic deposition were evaluated in the plastic s-AIT at a 30 L/min flow rate, followed by additional testing in the metal s-AIT to evaluate effects across a range of flow rates (from 10 to 100 L/min). Results: Actuator orifice was found to strongly influence regional extrathoracic deposition of a commercially available epinephrine HFA suspension pMDI aerosol, with smaller actuator orifices yielding reduced oral cavity deposition and increased distal-filter ( in vitro lung) deposition in both the plastic and metal s-AIT. Inhalation flow rate was found to strongly influence deposition in the metal s-AIT, with higher flow rates associated with reduced oral cavity deposition, increased pharynx/larynx deposition, and increased upper trachea deposition. Smaller orifices showed less variability in results as a function of inhaler insertion angle. Conclusions: Actuator orifice diameter (spanning 0.22–0.42 mm) can strongly influence regional deposition of an HFA epinephrine suspension pMDI aerosol within the extrathoracic region. Smaller actuator orifices may provide reduced oral cavity deposition and increased delivery to the lungs. Smaller actuator orifices may also reduce variability in extrathoracic deposition that is associated with patient use aspects such as inhaler insertion angle.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| 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".