API‐ILs Ionic Adducts: Solubility and Surface Activity Properties—En Route to New Paradigm in Drug Development

Two novel, structurally different perfluoroalkyl ionic liquids with bicyclic guanidinium cation have been synthesized and applied as a surfactant component for selected active pharmaceutical ingredients (APIs). The addition of perfluoroalkyl ionic liquid to hydrophobic APIs significantly improves their solubility. One of the key and characteristic properties of guanidine derivatives is their strong ability to chemisorb protons (proton affinity). This property enables them to form stable ionic-type aggregates (adducts) with selected hydrophobic APIs containing carboxylic groups. Therefore, these new compounds are, in fact, API-IL ionic adducts formed as hydrogen bond donor-acceptor systems. The obtained adducts are characterized by significantly better solubility than the initial APIs. The presence of perfluoroalkyl chains with unique surface-active properties enables to obtain a solubility of new adducts to reach level sufficient for typical ophthalmic preparations. (e.g., eye drops or lens care). The ionic API-IL adducts obtained in the described studies can be considered as examples of a new class of active derivatives with pharmaceutical potential.