Oral liquid formulation of levothyroxine is stable in breakfast beverages and may improve thyroid patient compliance
Open accessAbstract
Patients on treatment with levothyroxine (T4) are informed to take this drug in the morning, at least 30 min before having breakfast. A significant decrease of T4 absorption was reported, in fact, when T4 solid formulations are taken with food or coffee. According to preliminary clinical study reports, administration of T4 oral solution appears to be less sensitive to the effect of breakfast beverages on oral bioavailability. In the present study, stability of T4 oral solution added to breakfast beverages was investigated. A 1 mL ampoule of single-dose Tirosint® oral solution (IBSA Farmaceutici Italia, Lodi, Italy) was poured into defined volumes of milk, tea, coffee, and coffee with milk warmed at 50 °C, as well as in orange juice at room temperature. Samples were sequentially collected up to 20 min and analyzed by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The results of the study demonstrated that T4 is stable in all beverages after 20 min incubation. Demonstration of T4 stability is a prerequisite for a thorough evaluation of the effect of breakfast beverages on the bioavailability of T4 given as oral solution and for a better understanding of the reasons underlying a decreased T4 bioavailability administered as solid formulations.
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When the liquid LT4 preparation contained in these ampoules is added to breakfast beverages, the T4 content is stable for at least 20 minutes.
“When the liquid LT4 preparation contained in these ampoules is added to breakfast beverages the T4 content is stable for at least 20 minutes (117).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [117]
An in vitro study found that T4 was stable in coffee, milk, tea, and orange juice after 20 minutes of incubation at 50 °C.
“Bernareggi et al diluted liquid LT4 into several beverages (coffee, milk, tea, and orange juice) at 50 °C and evaluated the stability for up to 20 minutes (211). Liquid chromatography–tandem mass spectrometry revealed that T4 was stable in all beverages after 20 minutes of incubation.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [211]
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- Authors
- Bernareggi, A., Grata, E., Pinorini, M., & Conti, A.
- Affiliations
- IBSA Institut Biochimique (Switzerland) (CH)
- Alpine Foundation for Life Sciences (AFLS), Alpine Institute for Chemistry and Toxicology, Olivone CH-6718, Switzerland
- Corresponding author
- Bernareggi, Alberto
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2013-12-13
- Volume
- 5
- Issue
- 4
- Pages
- 621-633
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC3873683
- OpenAlex
- W2080018082
- Cited by
- 30
- References
- 15
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 7
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- levothyroxine, oral solution, drug stability, food-drug interactions, coffee, milk, orange juice, tea, medication adherence
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