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

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.