42
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.
Keywords Solubility · Macromolecules · Antimicrobial · Topical route · Oral
route · Nasal route
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
C.-H. Nguyen et al.
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.
Keywords Solubility · Macromolecules · Antimicrobial · Topical route · Oral
route · Nasal route
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
C.-H. Nguyen et al.