Kinetics of degradation of levothyroxine in aqueous solution and in solid state
Abstract
The kinetics of the deiodination of levothyroxine in aqueous solution were studied over the pH range 1 to 12. Temperature dependence of the reaction was also studied. The log k - pH profile indicated that the kinetics of deiodination include proton attack on the anion and dianion in acidic solution and water attack on the anion and dianion in alkaline solution. A possible mechanism of the deiodination was discussed. The solid-state stability of levothyroxine sodium was studied at elevated temperatures; and the compound was found to undergo deamination on heating. The decomposition follows biphasic first-order kinetics, with the most rapid decomposition occurring at the beginning of heating.
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The physical chemistry of electrolytic solutions
(1950) · Journal of the Franklin Institute · doi:10.1016/0016-0032(50)90436-4 · Cited by 3,034 · see citing works
Moore, J. W., Pearson, R. G., & Frost, A. A. (1961) · Andalas University Repository (Andalas University) · Cited by 2,347 · see citing works
Analytical profiles of drug substances
(1975) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600640947 · Cited by 1,498 · see citing works
Bourns, A. N., & Buncel, E. (1961) · Annual Review of Physical Chemistry · doi:10.1146/annurev.pc.12.100161.000245 · Cited by 418 · see citing works
Hine, J. S. (1960) · Annual Review of Physical Chemistry · doi:10.1146/annurev.pc.11.100160.000433 · Cited by 280 · see citing works
Reynolds, C. R. (2014) · Wiley eBooks · doi:10.1002/9781118660584.ese1861 · Cited by 165 · see citing works
DEIODINATION OF THE IODINATED AMINO ACIDS*
Stanbury, J. B. (1960) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1960.tb42820.x · Cited by 66 · see citing works
Grovenstein, E., & Aprahamian, N. S. (1962) · Journal of the American Chemical Society · doi:10.1021/ja00861a018 · Cited by 35 · see citing works
Brower, J. F., Toler, D. Y., & Reepmeyer, J. C. (1984) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600730937 · Cited by 24 · see citing works
Lippold, B. H., & Jf, L. (1981) · Archiv der Pharmazie · doi:10.1002/ardp.19813140612 · Cited by 5 · see citing works
Pitfalls in Studies ofin VitroDeiodination of Thyroxine
Jolín, T., de Escobar, G. M., & del Rey, F. E. (1966) · Endocrinology · doi:10.1210/endo-78-1-7 · Cited by 4 · see citing works
[Thyroxine deiodination studied with instrumental analytical methods].
Reviczky, A. L., & Sb, N. (1970) · PubMed · Cited by 1 · see citing works
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Gastrointestinal malabsorption of thyroxine
Virili, C., Antonelli, A., Santaguida, M. G., Benvenga, S., & Centanni, M. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00168 · Cited by 164 · see citing works
Pabla, D., Akhlaghi, F., & Zia, H. (2009) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.10.008 · Cited by 124 · see citing works
Cappelli, C., Pirola, I., Daffini, L., Formenti, A., Iacobello, C., Cristiano, A., Gandossi, E., Agabiti Rosei, E., & Castellano, M. (2016) · Thyroid · doi:10.1089/thy.2015.0422 · Cited by 80 · see citing works
The effect of excipients on the stability of levothyroxine sodium pentahydrate tablets
Patel, H., Stalcup, A., Dansereau, R., & Sakr, A. (2003) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(03)00387-9 · Cited by 55 · see citing works
Levothyroxine therapy in gastric malabsorptive disorders
Virili, C., Brusca, N., Capriello, S., & Centanni, M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.621616 · Cited by 52 · see citing works
TSH-Based Protocol, Tablet Instability, and Absorption Effects on L-T <sub>4</sub> Bioequivalence
Eisenberg, M., & Distefano, J. J. (2009) · Thyroid · doi:10.1089/thy.2008.0148 · Cited by 43 · see citing works
Oral liquid levothyroxine treatment at breakfast: a mistake?
Cappelli, C., Pirola, I., Gandossi, E., Formenti, A., & Castellano, M. (2014) · European Journal of Endocrinology · doi:10.1530/eje-13-0693 · Cited by 41 · see citing works
Centanni, M., Duntas, L., Feldt-Rasmussen, U., Koehrle, J., Peeters, R. P., Razvi, S., Trimboli, P., & Virili, C. (2025) · European Thyroid Journal · doi:10.1530/etj-25-0123 · Cited by 38 · see citing works
Levothyroxine treatment and gastric juice pH in humans: the proof of concept
Virili, C., Bruno, G., Santaguida, M. G., Gargano, L., Stramazzo, I., De Vito, C., Cicenia, A., Scalese, G., Porowska, B., Severi, C., et al. (2022) · Endocrine · doi:10.1007/s12020-022-03056-1 · Cited by 22 · see citing works
Levothyroxine sodium pentahydrate tablets – formulation considerations
Kaur, N., & Suryanarayanan, R. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.08.006 · Cited by 19 · see citing works
Kocic, I., Homsek, I., Dacevic, M., Parojcic, J., & Miljkovic, B. (2011) · AAPS PharmSciTech · doi:10.1208/s12249-011-9660-8 · Cited by 19 · see citing works
Impact of hydration state and molecular oxygen on the chemical stability of levothyroxine sodium
Hamad, M. L., Engen, W., & Morris, K. R. (2015) · Pharmaceutical Development and Technology · doi:10.3109/10837450.2013.862635 · Cited by 14 · see citing works
Investigating the influence of excipients on the stability of levothyroxine sodium pentahydrate
Kaur, N., & Suryanarayanan, R. (2021) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.1c00217 · Cited by 13 · see citing works
Romanelli, R. J., Nimbal, V., Dutcher, S. K., Pu, X., & Segal, J. B. (2017) · Annals of Pharmacotherapy · doi:10.1177/1060028017705393 · Cited by 5 · see citing works
Agu, R. U., Mactavish, J., K. Yeung, P., & Imran, S. A. (2016) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2016.1115012 · Cited by 4 · see citing works
- Authors
- Won, C. M.
- Corresponding author
- Won, Chong Min
- Venue
- Pharmaceutical Research
- Published
- 1992-01
- Volume
- 9
- Issue
- 1
- Pages
- 131-137
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W1600533342
- Cited by
- 69
- References
- 12
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 1 · 2013: 7 · 2012: 2
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Thermal and Kinetic Analysis
- Keywords
- levothyroxine, deiodination, degradation kinetics, pH dependence, temperature dependence, water attack, reaction mechanism, levothyroxine sodium, solid-state stability, thermal decomposition, deamination, aqueous solutions
- MeSH terms
- Chromatography, High Pressure Liquid, Dosage Forms, Drug Stability, Hydrogen-Ion Concentration, Iodine, Solubility, Solutions, Thyroxine, Water, Molecular Structure
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