Ionic Liquids and salts from Ibuprofen as promising innovative formulations of an old drug.

Herein we report the synthesis of novel ionic liquids (ILs) by combination of Ibuprofen as anion with biocompatible ammonium, imidazolium and pyridinium cations. The synthetic methodology consisted in the acid-base reaction of neutral Ibuprofen with cation hydroxides, which were previously prepared by anion exchange from the corresponding halide salts with Amberlyst A-26(OH). In comparison with the parent drug, the plethora of synthesized compounds display very attractive physicochemical properties such as higher solubility in water and biological fluids and a smaller degree of polymorphism which in some cases was completely eliminated. With the exception of [C16Pyr][Ibu] and [N1,1,2,2OH1][Ibu], the majority of the other salts did not affect the viability of normal human dermal fibroblasts or the viability of ovarian carcinoma (A2780) cell lines. Interestingly, the cytotoxicity of [C16Pyr][Ibu] might be ascribed to its cation, once [C16Pyr]Cl showed IC50 values < 100 and 2.2 ± 0.1 µM for fibroblasts and A2780 cell line, respectively. Thus, in the future these Ibuprofen-based ionic liquids may be very promising lead candidates for the development of new and highly effective formulations of this drug.