Solubility studies on the system of trihexyl(tetradecyl)phosphonium bis[(trifluoromethyl)sulfonyl]amide) ionic liquid and pharmaceutical and bioactive compounds

The solubility of pharmaceutical and bioactive compounds in non-volatile ionic liquids can lead to their usage in pharmaceutical processing, competing directly with flammable chemicals used routinely in pharmaceutical development. The solubility of a variety of drugs and bioactive compounds, namely N-acetyl-l-cysteine, isoniazid, pyrazine-2-carboxamide (pyrazine-2-carboxamide), coumarin, 4-hydroxycoumarin, 4'-isobutylacetophenone, ibuprofen and thymoquinone, was tested in a hydrophobic ionic liquid (trihexyl(tetradecyl)phosphonium bis[(trifluoromethyl)sulfonyl]amide). The solid-liquid equilibrium (SLE) measurements have been performed using a dynamic (synthetic) method. Glass transition temperature, T_g and heat capacity at glass transition temperature, δC_p,g, of 4'-isobutylacetophenone and (trihexyl(tetradecyl)phosphonium bis[(trifluoromethyl)sulfonyl]amide) were acquired using a differential scanning calorimetry (DSC). Dependence between hydrophobicity and melting point directs the solubility of the solutes studied in [P_6,6,6,14][NTf₂]. 4'-Isobutylacetophenone, thymoquinone, coumarin and ibuprofen exhibited the best solubility in the IL due to their hydrophobicity. Then, N-acetyl-l-cysteine was found to be less soluble, and later on isoniazid, 4-hydroxycoumarin and pyrazinecarboxamide showed limited solubility in IL. The solid-liquid phase equilibria of all investigated systems were described using the six different correlation equations. Considering the correlation of the phase equilibrium data, the satisfactory results which revealed a good description with an acceptable standard deviation temperature range were collected for systems with: N-acetyl-l-cysteine, coumarin, thymoquinone and ibuprofen.