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Abstract

Finding alternative solvents for industrial processes, such as chemical synthesis or extraction of biologically active molecules that are less toxic and more environmentally friendly than the organic solvents used up to now, is a major societal issue. These alternative solvents are often described as “green, biodegradable” solvents. Deep eutectic solvents, which are mixtures of simple and often naturally occurring compounds, have been extensively studied in this regard. Among their possible applications, there has been increasing interest in their use for the preparation of pharmaceutical formulations. Indeed, by changing the nature and ratio of their components, deep eutectic solvents can be adapted to a wide range of active molecules, from poorly soluble small molecules to labile macromolecules. The use of deep eutectic solvents to solubilize active molecules with low aqueous solubility and/or low permeability could be an alternative approach to increase their dissolution and in vivo absorption. This could result in significant increases of bioavailability or enhanced therapeutic efficacy of currently marketed drugs. Moreover, deep eutectic solvents can be used to limit phenomena like polymorphism or degradation which present a challenge to drug formulation. However, despite being generally described as biodegradable and nontoxic due to the nature of their constituents, the safety of deep eutectic solvents, which possess both novel physicochemical and biological properties, cannot be taken for granted and must therefore be carefully studied during development stages. Therefore, this chapter presents not only recent progress in the application of deep eutectic solvents in the development of formulations for improving therapeutic efficacy by different routes of administration but also studies that have been undertaken to investigate the toxicity of deep eutectic solvents to both living organisms and the environment.

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Abbreviations

A:

Acetamide

AA:

Acrylic acid

ACA:

Aconitic acid

Arg:

Arginine

β-ala:

β-alanine

B:

Betaine

C:

Choline

CA:

Citric acid

CC:

Choline chloride

CH:

Cholinium hydroxide

DEEAC:

N,N-diethylethanolammonium chloride

EG:

Ethylene glycol

F:

Fructose

G:

Glucose

GA:

Glycolic acid

GE:

Geranate

GL:

Glycerol

GLA:

Glutamic acid

GLN:

Glutamine

HBA :

Hydrogen bond acceptor

HBD :

Hydrogen bond donor

LA:

Lactic acid

LAU:

Lauric acid

MA:

Malic acid

MEA:

Maleic acid

MOA:

Malonic acid

OA:

Oxalic acid

P:

Proline

PD:

1,2-Propanediol (propylene glycol)

PHE:

Phenylalanine

S:

Sucrose

TA:

Tartaric acid

TEAC:

Tetraethylammonium chloride

TEG:

Triethylene glycol

TBAB:

Tetrabutylammonium bromide

TPAB:

Tetrapropylammonium bromide

U:

Urea

W:

Water

X:

Xylitol

ZC:

Zinc chloride

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Acknowledgments

The authors thank the French Embassy in Vietnam for the PhD fellowship of Canh-Hung Nguyen and the French National Research Agency (ANR) for the funding of the project ParasiDES (ANR-19-CE18-0027).

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Correspondence to Gillian Barratt or François-Xavier Legrand .

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Nguyen, CH., Augis, L., Fourmentin, S., Barratt, G., Legrand, FX. (2021). Deep Eutectic Solvents for Innovative Pharmaceutical Formulations. In: Fourmentin, S., Costa Gomes, M., Lichtfouse, E. (eds) Deep Eutectic Solvents for Medicine, Gas Solubilization and Extraction of Natural Substances. Environmental Chemistry for a Sustainable World, vol 56. Springer, Cham. https://doi.org/10.1007/978-3-030-53069-3_2

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