Cited by 19Analytical Methods in PharmaceuticalsPharmaceutical Quality and CounterfeitingCrystallization and Solubility Studies

Levothyroxine sodium pentahydrate tablets – formulation considerations

Kaur, Navpreet, Suryanarayanan, Raj·2021·Journal of Pharmaceutical Sciences

Abstract

Even though levothyroxine sodium pentahydrate tablets have been in the market since 1955, there continue to be recalls due to sub potency. We have comprehensively reviewed the factors affecting its stability in solid oral dosage forms. A compilation of marketed formulation compositions enabled the identification of the potential 'problem excipients'. Two excipient properties, hygroscopicity and microenvironmental acidity, appeared to be responsible for inducing drug instability. In drug products, depending on the formulation composition and storage conditions, the pentahydrate can dehydrate to highly reactive levothyroxine sodium monohydrate, or undergo salt disproportionation to the free acid form of the drug. The USP assay method (HPLC based) is insensitive to these different physical forms of the drug. The influence of physical form of levothyroxine on its chemical stability is incompletely understood. The USP has five product-specific dissolution tests reflecting the complexity in its evaluation.

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Crossref · 10.1016/j.xphs.2021.08.006

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231 of 231 references verified0 citation errors · 0 not checkable

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  • LT4 is one of the most frequently recalled products from the market in several countries, mostly for issues in maintaining potency during shelf life.

    “LT4 is even one of the most frequently recalled products from the market in several countries, mostly for issues in maintaining potency during the shelf life (26).”
  • Gradual loss of non-stoichiometric five crystal water molecules yielding LT4 monohydrate occurs under realistic storage conditions and, along with light exposure and high temperatures, may contribute to chemical decomposition of LT4.

    “A further factor influencing stability and decomposition of LTSS is the gradual loss of the non-stoichiometric number of five crystal water molecules yielding LT4 monohydrate. This process already occurs under realistic storage conditions, and along with light exposure and high temperatures, may contribute to the chemical decomposition of LT4 (26).”

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Authors
Kaur, N., & Suryanarayanan, R.
Affiliations
University of Minnesota (US)
Corresponding author
Suryanarayanan, Raj
Venue
Journal of Pharmaceutical Sciences
Publisher
Elsevier BV
Published
2021-12
Volume
110
Issue
12
Pages
3743-3756
ISSN
0022-3549 (ISSN-L)
OpenAlex
W3191883233
Cited by
19
References
237
Citations by year
2026: 1 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 3
FWCI
0.42
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Pharmaceutical Sciences (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pharmaceutical Quality and Counterfeiting
  • Physical Sciences › Materials Science › Materials Chemistry › Crystallization and Solubility Studies
Keywords
tablet formulation, drug stability, drug recall, pharmaceutical excipients, hygroscopicity, dehydration, dissolution testing, storage conditions
MeSH terms
Drug Compounding, Drug Stability, Excipients, Solubility, Tablets, Thyroxine

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