An Exploration of Factors Affecting <i>In Vitro</i> Deposition of Pharmaceutical Aerosols in the Alberta Idealized Throat
Bibliographic record
Abstract
Background: The development of accurate in vitro—in vivo correlations requires the consideration of a number of factors in vitro, including the emulation of upper airway geometry, inhalation maneuver, inhaler orientation, and environmental conditions. In this study, we examine the effects of inhaler insertion angle and humidity on deposition from a number of marketed inhalers. Methods: Three dry-powder inhalers (DPIs; Pulmicort® Turbuhaler®, Budelin® Novolizer®, and Easyhaler® Budesonide) were examined at two insertion angles, one with the inhaler directed toward the back of the oral cavity, the other with the inhaler directed toward the tongue. Three pressurized metered-dose inhalers (pMDIs; QVAR®, Ventolin® Evohaler®, and Flovent® HFA) were examined considering the joint effects of insertion angle (as above) and relative humidity at low (15%–25%) and high (>95%) conditions. Deposited drug masses in an Alberta Idealized Throat and downstream filter were quantified through ultraviolet spectroscopy. Results and Conclusions: Three of six inhalers showed sensitivity to insertion angle. When directed toward the tongue versus the back of the mouth, the filter dose decreased from 21.9% to 15.6% (percent delivered dose) for Easyhaler Budesonide (p < 0.001), from 46.5% to 26.0% for Ventolin Evohaler (p < 0.001), and from 56.7% to 35.7% for Flovent HFA (p < 0.001) for tests at ambient laboratory humidity. Sensitivity to insertion angle and increases in total lung dose variability may be reduced in future products using larger diameter mouthpieces and smaller particles for DPIs and lower-momentum sprays for pMDIs. Humidity influenced deposition from Ventolin Evohaler and Flovent HFA. When oriented toward the back of the oral cavity, the filter dose decreased from 46.5% to 36.9% for Ventolin Evohaler (p = 0.005) and from 56.7% to 44.2% for Flovent HFA (p < 0.001) at high humidity relative to low. High humidity may cause a reduction in total in vitro lung doses for some pMDI aerosols.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".