Development of Intranasal Levothyroxine Powder Delivery for Hypothyroidism
Bibliographic record
Abstract
Abstract Background: Hypothyroidism affects 3-5% of the general population with oral levothyroxine (LT4) being the predominant replacement therapy. However, significant proportion of hypothyroid patients are unable to absorb oral replacement leading to therapeutic failure and may require injectable thyroxine. Objectives: To develop non-invasive, less costly, and patient-friendly LT4 nasal delivery alternative using mucoadhesive polymers: chitosan and hydroxypropylmethylcellulose (HPMC). Methods: Six nasal LT4 formulations were developed with either chitosan or hydroxypropyl methylcellulose as mucoadhesive. The formulations were prepared through freeze-drying by varying the drug to polymer ratio (1:1, 1:3, and 1:5). The percentage drug yield was calculated by analyzing the weight of the formulation pre- and post-freeze drying. HPLC analysis was conducted to determine the amount of LT4 loaded in each formulation. Furthermore, the surface morphology, particle size, zeta potential, differential scanning calorimetry, X-ray diffraction as well as the in vitro release were assessed to determine the physicochemical properties and release characteristics of the formulations, respectively. Results: Both percentage drug loading and yield were > 70% for all the formulations. The freeze-dried formulations displayed a compact needle-like surface morphology. LT4-chitosan formulations, 1:1, 1:3, and 1:5 had mean particle size of 2.45 ± 0.88 µm, 2.76 ± 1.38 µm, and 1.59 ± 0.27 µm, respectively. Mean particle sizes for 1:1, 1:3, and 1:5 LT4-HPMC formulations were 0.56 ± 0.02 µm, 0.22 ± 0.06 µm, and 0.46 ± 0.04 µm. Zeta potential for LT4-chitosan formulation 1:1, 1:3, and 1:5 were -18.7 ± 1.00 mV, -16.2 ± 0.79 mV, and -19.17 ± 1.01 mV, respectively. LT4-HPMC 1:1, 1:3, and 1:5 formulations had zeta charges of -11.66 ± 3.16 mV, -6.06 ± 3.92 mV, and -9.53 ± 1.68 mV, respectively. Differential calorimetric analysis confirmed drug-polymer integration in all formulations, and X-ray powder diffraction showed both chitosan and HPMC formulations as crystalline configuration. The formulations with the highest in vitro release were LT4-HPMC 1:3 and LT4-chitosan 1:5. Conclusions: Results of this study suggest that both chitosan and HPMC can be used as sustained release polymers for the intranasal delivery of LT4.
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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) | 0.000 | 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 | 0.000 | 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".