Ionic Levothyroxine Formulations: Synthesis, Bioavailability, and Cytotoxicity Studies

Thyroid diseases affect a considerable portion of the population, with hypothyroidism being one of the most commonly reported thyroid diseases. Levothyroxine (T4) is clinically used to treat hypothyroidism and suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, an attempt to improve T4 solubility is made through the synthesis of ionic liquids (ILs) based on this drug. In this context, [Na][T4] was combined with choline [Ch]⁺ and 1-(2-hydroxyethyl)-3-methylimidazolium [C₂OHMiM] ⁺ cations in order to prepare the desired T4-ILs. All compounds were characterized by NMR, ATR-FTIR, elemental analysis, and DSC, aiming to check their chemical structure, purities, and thermal properties. The serum, water, and PBS solubilities of the T4-ILs were compared to [Na][T4], as well as the permeability assays. It is important to note an improved adsorption capacity, in which no significant cytotoxicity was observed against L929 cells. [C₂OHMiM][T4] seems to be a good alternative to the commercial levothyroxine sodium salt with promising bioavailability.