New API-ILs derived from Indomethacin and Mebendazole

The efficiency of a drug or Active Pharmaceutical Ingredient (API) is highly dependent on its bioavailability, the degree and rate at which the drug is absorbed into the organism.¹ APIs employed in the formulation of drugs are usually found in the crystalline form, which present a series of drawbacks, such as low water solubility, polymorphism or low lipophilicity.

Due to the unique properties of ionic liquids, in the last few years new ILs incorporating APIs on their structure (API-ILs) have been developed as an alternative to resolve the inconveniences produced by drugs in solid state.

In this communication, the transformation of two solid APIs into new API-ILs is reported. Due to their low solubility in water and their high susceptibility of being transformed into ionic liquids, the two APIs selected were Indomethacin and Mebendazole. The selection of the counterion of the ionized APIs was done looking for ions with high bioavailability and low toxicity, such as those derived from tetramethylguanidine (TMG), 2-dimethylaminoethanol (DMEA), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-Diazabicyclo[2.2.2]octane (TED), p-toluensulfonic acid, glycolic acid, methanesulfonic acid and saccharine.

The synthesis of the API-ILs was carried out by direct treatment of the API with the corresponding acid or base selected. Finally, a solubility test of the API-ILs synthesized, was approached.