Exploring the Benefits of Active Pharmaceutical Ingredients as Ionic Liquids for Indomethacin and Mebendazole

Some of the main challenges that the pharmaceutical industry has to face is to overcome the physicochemical problems that many drugs present due to polymorphism, low solubility, and low bioavailability. Recently, it has been shown that the combination of solid, poorly water-soluble Active Pharmaceutical Ingredients (APIs) with suitable counter-ions to give liquid forms (API-ILs) can resolve these limitations. The purpose of this study was to explore the transformation of Indomethacin and Mebendazole, two solid, poorly water-soluble APIs into new API-ILs. Their structures were selected by their pharmaceutical interest, their susceptibility of being transformed into API-ILs (either to form the cation or the anion), and their limited bioavailability, mainly due to its low solubility. The counterions were carefully chosen aiming for high biocompatibility, low toxicity and high water solubility such as those derived from DMEA, TMG, DBU, TED, p-toluensulfonic acid, glycolic acid, methanesulfonic acid and saccharine. The synthesis was carried out by direct treatment of the API with the corresponding selected acid or base. Solubility tests showed a high increase of water solubility for all the salts synthesised, especially for the API-ILs derived from indomethacin which showed a water solubility in the range of 185 and 218 mg/mL, around 75000-hold higher than free drug indomethacin.