Thyroid hormone (levothyroxine) replacement via the respiratory route by inhalation:<i>in vitro</i>exploratory studies
Bibliographic record
Abstract
OBJECTIVES: To conduct proof of principle studies that will enable development of noninvasive (respiratory) delivery systems for levothyroxine (T4). METHODS: Preformulation (solubility, stability), formulation and biopharmaceutical (in vitro absorption, transport, gene expression) studies were conducted. Calu-3 cell line was used for permeation studies. RESULTS: Solubility profiles of T4 were established in aqueous (PBS, HBSS, isotonic saline) and non-aqueous solvents (PEG 400, PEG 600, propylene glycol, glycerine). Transport of the compound across Calu-3 cells suggested involvement of active transport systems. This correlated with expression of thyroxine transporters (MCT8, MCT10, OATP1A2, LAT1 and LAT2) in the cell line. Diffusion characteristics showed significant absorption with no detection of T4 metabolite (triiodothyronine). Formulation studies revealed that stable formulations could be prepared using a combination of aqueous and non-aqueous solvents. CONCLUSIONS: Results of the studies indicated that T4 can be absorbed effectively from the respiratory mucosa. Factors affecting stability such as pH and temperature should be taken into account during formulation development of this compound for the respiratory route.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".