44
and more interest because of their ease of use and better acceptability. This brings
new challenges to formulation and a need for suitable additives.
Ionic liquids (IL) and deep eutectic solvents (DES) have been studied for over a
century, but interest in their pharmaceutical applications is more recent (Agatemor
et al. 2018; Adawiyah et al. 2016). Both solvents are mixtures of low-molecularweight organic salts, containing a hydrogen bond donor (HBD) and a hydrogen bond
acceptor (HBA), that are liquid below 100 °C. In 2011, Choi et al. put forward the
concept of natural deep eutectic solvents (NADES) composed of amino acids, sugars,
sugar alcohols, and polyalcohols that are found in living cells (Choi et al. 2011). They
postulated that these compounds could represent a “missing link” between aqueous
and lipophilic media and provide an environment that would allow cells to survive in
extreme conditions such as dehydration. These compositions can be considered as
“green solvents” that do not carry the same risks of toxicity and handling as traditional
organic solvents (Durand et al. 2016; Vanda et al. 2018). As such, they have numerous
applications in pharmaceutical formulations, which will be detailed in this chapter.
2.1.1 Definitions and Components
The terms “ionic liquid” and “deep eutectic solvent” are often used interchangeably,
but there are differences between the two systems (see correspondence arising from
Banerjee et al. 2018a; from Rogers and Gurau 2018; and from Banerjee et al. 2018b).
Although both can be considered as low transition temperature mixtures, there are
differences in the way in which they are obtained (Durand et al. 2016). Deep eutectic
solvents are prepared by mixing two molecules, and the driving force for their formation is hydrogen bonding. On the other hand, ionic liquids are organic or inorganic
salts whose behavior is mainly defined by ionic interactions. Within the category of
deep eutectic solvents, some authors have proposed a subclass called natural deep
eutectic solvents (NADES) composed of molecules that are found within cells, as
mentioned above (Choi et al. 2011; Vanda et al. 2018). In this chapter, we will concentrate on deep eutectic solvents, although ionic liquids will be included when they
have been compared with deep eutectic solvents in the same experimental system.
As can be seen in Tables 1, 2, 3, 4, 5 and 6, by far, the most frequently used
hydrogen bond acceptor is choline or choline chloride, while the hydrogen bond
donors are often organic acids or sugars, or urea.
2.1.2 Physicochemical Properties: Characterization of Deep
Eutectic Solvents
The physicochemical characterization of deep eutectic solvents systems is based
around thermal and rheological properties. The low transition temperature can be
checked by simple measurement of melting point, but differential scanning calorimetry gives a more accurate picture of the thermal behavior.
C.-H. Nguyen et al.
and more interest because of their ease of use and better acceptability. This brings
new challenges to formulation and a need for suitable additives.
Ionic liquids (IL) and deep eutectic solvents (DES) have been studied for over a
century, but interest in their pharmaceutical applications is more recent (Agatemor
et al. 2018; Adawiyah et al. 2016). Both solvents are mixtures of low-molecularweight organic salts, containing a hydrogen bond donor (HBD) and a hydrogen bond
acceptor (HBA), that are liquid below 100 °C. In 2011, Choi et al. put forward the
concept of natural deep eutectic solvents (NADES) composed of amino acids, sugars,
sugar alcohols, and polyalcohols that are found in living cells (Choi et al. 2011). They
postulated that these compounds could represent a “missing link” between aqueous
and lipophilic media and provide an environment that would allow cells to survive in
extreme conditions such as dehydration. These compositions can be considered as
“green solvents” that do not carry the same risks of toxicity and handling as traditional
organic solvents (Durand et al. 2016; Vanda et al. 2018). As such, they have numerous
applications in pharmaceutical formulations, which will be detailed in this chapter.
2.1.1 Definitions and Components
The terms “ionic liquid” and “deep eutectic solvent” are often used interchangeably,
but there are differences between the two systems (see correspondence arising from
Banerjee et al. 2018a; from Rogers and Gurau 2018; and from Banerjee et al. 2018b).
Although both can be considered as low transition temperature mixtures, there are
differences in the way in which they are obtained (Durand et al. 2016). Deep eutectic
solvents are prepared by mixing two molecules, and the driving force for their formation is hydrogen bonding. On the other hand, ionic liquids are organic or inorganic
salts whose behavior is mainly defined by ionic interactions. Within the category of
deep eutectic solvents, some authors have proposed a subclass called natural deep
eutectic solvents (NADES) composed of molecules that are found within cells, as
mentioned above (Choi et al. 2011; Vanda et al. 2018). In this chapter, we will concentrate on deep eutectic solvents, although ionic liquids will be included when they
have been compared with deep eutectic solvents in the same experimental system.
As can be seen in Tables 1, 2, 3, 4, 5 and 6, by far, the most frequently used
hydrogen bond acceptor is choline or choline chloride, while the hydrogen bond
donors are often organic acids or sugars, or urea.
2.1.2 Physicochemical Properties: Characterization of Deep
Eutectic Solvents
The physicochemical characterization of deep eutectic solvents systems is based
around thermal and rheological properties. The low transition temperature can be
checked by simple measurement of melting point, but differential scanning calorimetry gives a more accurate picture of the thermal behavior.
C.-H. Nguyen et al.