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Ionic Levothyroxine Formulations: Synthesis, Bioavailability, and Cytotoxicity Studies.

António Barreira1, Andreia F M Santos1, Madalena Dionísio1

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Researchers synthesized novel ionic liquids (ILs) based on levothyroxine (T4) to enhance drug solubility. The T4-ILs demonstrated improved solubility and bioavailability, offering a promising alternative for hypothyroidism treatment.

Keywords:
T4 based ionic liquids (T4-ILs)cytotoxicityionic formulationslevothyroxine (T4)permeabilitysolubility

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Area of Science:

  • Pharmaceutical Chemistry
  • Materials Science
  • Endocrinology

Background:

  • Thyroid diseases, particularly hypothyroidism, are prevalent, necessitating effective treatments.
  • Levothyroxine (T4) is the standard treatment for hypothyroidism but faces solubility challenges.
  • Ionic liquids (ILs) offer potential for improving drug properties.

Purpose of the Study:

  • To synthesize novel ionic liquids incorporating levothyroxine (T4) to enhance its solubility.
  • To characterize the synthesized T4-based ionic liquids (T4-ILs).
  • To evaluate the solubility, permeability, and cytotoxicity of the T4-ILs.

Main Methods:

  • Synthesis of T4-ILs by combining sodium levothyroxine ([Na][T4]) with choline [Ch]+ and 1-(2-hydroxyethyl)-3-methylimidazolium [C2OHMiM]+ cations.
  • Characterization using NMR, ATR-FTIR, elemental analysis, and Differential Scanning Calorimetry (DSC).
  • Solubility studies in serum, water, and PBS; permeability assays; and cytotoxicity assessment against L929 cells.

Main Results:

  • Successful synthesis and characterization of T4-ILs, confirming their chemical structures and thermal properties.
  • Significantly improved solubility of T4-ILs in serum, water, and PBS compared to [Na][T4].
  • No significant cytotoxicity observed for T4-ILs, with [C2OHMiM][T4] showing promising permeability.

Conclusions:

  • Ionic liquid formulation of levothyroxine (T4) effectively enhances drug solubility and bioavailability.
  • The synthesized [C2OHMiM][T4] ionic liquid represents a potentially superior alternative to commercial levothyroxine sodium salt.
  • This approach holds promise for developing improved drug delivery systems for hypothyroidism management.