Deep eutectic solvents (DES) are mixtures of two or more solid compounds which form a liquid phase at room temperature at a particular composition [1]. DES are formed by hydrogen-bond-donor (HBD) and hydrogen bond acceptor (HBA) species or Lewis acids and bases. The decrease in the melting point of the mixture (much lower than in an ideal mixture) is due to a strong interaction between the different species, leading to a more disordered structure that remains liquid at room temperature, presenting a relatively low vapour pressure [2]. DES are formed by two or more compounds and, particularly those of natural origin, are non-toxic, low-cost and can be prepared pure straightforward (simply mixing the compounds) without further purification steps. Because of the large number of possible HBA and HBD combinations, DES can be also tailor-made. DES can be hydrophobic and hydrophilic. DES have been used as solvents in many processes such as extraction and separation [3], chemical reactions [4, 5], gas absorption [6], metal plating [7], metal absorption [8], nanoparticle (NP) formation [9] and drug delivery [10].

Active pharmaceutical Ingredients (API) can be also dissolved into DES or can form readily DES with some natural substances forming Therapeutic Deep Eutectic solvents (THEDES). When the API is incorporated into the DES, it is in liquid form increasing its solubility and/or dissolution rate. The use of DES in the preparation of drug formulations to maintain APIs in liquid phase avoids polymorphism formation and leads to a better therapeutically action of the drug.

CO2 exhibits poor solubility in water under normal operating conditions but high solubility in DES, therefore hydrophobic DES have been used in CO2 capture processes [6]. There have also been some attempts to combine DES and scCO2 in the preparation of drug formulations, although this area is relatively unexplored.

We currently research the combined use of supercritical CO2 (scCO2) technology and the use of natural Deep Eutectic Solvents (DES) for the effective and green preparation of advanced drug delivery systems.

[1] S. Fourmentin, M. Gomes, E. Lichtfouse, Deep Eutectic Solvents for Medicine, Gas Solubilization and Extraction of Natural Substances, 2020.

[2] K. Xin, I. Roghair, F. Gallucci, M. van Sint Annaland, Total vapor pressure of hydrophobic deep eutectic solvents: Experiments and modelling, Journal of Molecular Liquids, 325 (2021) 115227.https://doi.org/10.1016/j.molliq.2020.115227

[3] D.J.G.P. van Osch, C.H.J.T. Dietz, S.E.E. Warrag, M.C. Kroon, The Curious Case of Hydrophobic Deep Eutectic Solvents: A Story on the Discovery, Design, and Applications, ACS Sustainable Chemistry & Engineering, 8 (2020) 10591-10612.10.1021/acssuschemeng.0c00559

[4] S. Khandelwal, Y.K. Tailor, M. Kumar, Deep eutectic solvents (DESs) as eco-friendly and sustainable solvent/catalyst systems in organic transformations, Journal of Molecular Liquids, 215 (2016) 345-386.https://doi.org/10.1016/j.molliq.2015.12.015

[5] L. Longo Jr, M. V. Craveiro, Deep Eutectic Solvents as Unconventional Media for Multicomponent Reactions, Journal of the Brazilian Chemical Society, 29 (2018).10.21577/0103-5053.20180147

[6] F.P. Pelaquim, A.M. Barbosa Neto, I.A.L. Dalmolin, M.C.d. Costa, Gas Solubility Using Deep Eutectic Solvents: Review and Analysis, Industrial & Engineering Chemistry Research, 60 (2021) 8607-8620.10.1021/acs.iecr.1c00947

[7] E.L. Smith, A.P. Abbott, K.S. Ryder, Deep Eutectic Solvents (DESs) and Their Applications, Chemical Reviews, 114 (2014) 11060-11082.10.1021/cr300162p

[8] G. Zante, M. Boltoeva, Review on Hydrometallurgical Recovery of Metals with Deep Eutectic Solvents, Sustainable Chemistry, 1 (2020) 238-255

[9] A. Abo-Hamad, M. Hayyan, M.A. AlSaadi, M.A. Hashim, Potential applications of deep eutectic solvents in nanotechnology, Chemical Engineering Journal, 273 (2015) 551-567.https://doi.org/10.1016/j.cej.2015.03.091

[10] S. Emami, A. Shayanfar, Deep eutectic solvents for pharmaceutical formulation and drug delivery applications, Pharm Dev Technol, 25 (2020) 779-796.10.1080/10837450.2020.1735414