Computational study of hydroxides of cholinium and tetramethylammonium derivatives as biofriendly ionic liquids for improved drug solubility and delivery

Low aqueous solubility of non-steroidal anti-inflammatory drugs (NSAIDs) is a significant limitation to their therapeutic application as it leads to large dosage consumption hence, increased risk of side effects. Herein, we investigated the co-solvency potentials of some ionic liquids (ILs) derived from Cholinium and Tetramethylammonium structural frameworks, for three NSAIDs: Ibuprofen (IBP), Ketoprofen (KTP) and Naproxen (NPR), using DFT-wB97XD with cc-pVTZ basis set. We probed the electronic interactions, interaction feasibility, electronic absorption and hydration tendencies of the drug-IL systems using some quantum chemical and solvation descriptors. Performances of the ILs were assessed in the presence and absence of ⁻OH to determine the role of this ion to their co-solvency behavior. The effect of replacing the nitrogen component of the ILs with phosphorus and oxygen was also studied. The results revealed that the studied ILs can significantly enhance the aqueous solubility of the drugs, irrespective of the presence of ⁻OH ion. However, their interactions with the drugs were more favourable in the absence of this ion. Also, the presence of ⁻OH impacted drug activity and choice of interacting orbitals. Replacement of N with P and O in the IL structures was found to promote interaction particularly in the absence of ⁻OH, with a slight reduction in solubilisation power. The presence of residual water molecules could reduce the viscosity of the ionic liquids and consequently enhance the solubility and delivery of the drugs. Performances of the Cholinium and Tetramethylammonium based ILs series were comparable but the Cholinium-based liquids displayed better cosolvency potential. We conclude that the studied IL structures are promising candidates for promoting the solubility and administrability of sparingly soluble drugs.