(35b) Natural Deep Eutectic Solvents As Enhanced Solubilizes

In recent years ionic liquids (IL) and recently dee eutectic solvents (DES) have been considered for chemical process applications such as gas capture and separation, biocatalysts, metal electropolishing and extraction, purifying and manufacturing biodiesel and many other processes are being considered to utilize these materials. DES reach to significant depression in melting points compared to their neat constituents when they are mixed in certain molar mixing ratios. They are considered as designer solvents since they offer tuneable physicochemical properties according to process needs. In this work, other than the utilization of these materials in more conventional chemical processes, they have been considered as delivery vehicles for commonly used water insoluble active pharmaceutical ingredient (API).

In this work, the solvation and solubilization of selected water insoluble API such as lidocaine (Ld) and ibuprofen (Ib) in alanine-based (Al) natural deep eutectic solvents (NADES) was studied using a combined experimental and theoretical considering quantum chemistry (density functional theory – DFT) approach. Al being hydrogen bond acceptor (HBA) and it was mixed with natural based organic acids such as oxalic acid (Oa), tartaric acid (Ta) and glutamic acid (Ga) as hydrogen bond donors (HBD). The optimum molar mixing ratios were calculated with COSMO-RS and structures with corresponding mixing ratios were built in Avogadro software. DFT simulations were carried out with ORCA DFT code and for the post DFT analysis MultiWFN code was used to carry out quantum theory atom-in-a-molecule (QT-AIM) analysis to infer on the intermolecular forces between the API and NADES with particular attention to hydrogen bonding distribution, bond critical points/paths, established bonding strength between API and NADES interaction sites, topological properties and interaction mechanism. The results of the DFT simulations were used to predict the API solubility in NADES environment in COSMO-RS calculations that uses group contribution method. Furthermore, experimental techniques such as UV-VIS and mass spectrometry analysis were used to obtain the maximum API solubility in the studied NADES and the results were compared against the DFT simulations and COSMO-RS predictions.

The reported results show the nanoscopic properties that confirm these solvents as suitable materials for anaesthetics drug delivery in liquid phase with NADES and exceptional solubility of Ib within the proposed NADES structures at room temperature. Solvent optimization technique carried out to study the blending possibilities of the studied organic acids as HBD and additional HBA (arginine - Ar) to explore the effect of solubility enhancement for Ld and Ib.