69
glycerol, sugars, or sugar alcohols (Jeliński et al. 2019a). They reported both
experimental results and theoretical determinations of thermodynamic parameters
using the conductor-like screening model for real solvents (COSMO-RS) protocol.
The solvent composed of choline chloride and glycerol in a 1:1 molar ratio gave the
highest solubility, and in general, equimolar proportions were the best solvents. In
the theoretical model, these mixtures were found to have the lowest enthalpy.
Therapeutic Deep Eutectic Solvents
It is possible that an active molecule can itself act as a component of a deep eutectic
solvent. As early as 1998, Stott et al. combined the nonsteroidal anti-inflammatory
drug ibuprofen with a number of terpenes, including menthol and thymol, to form
eutectic mixtures in an attempt to improve the transdermal penetration of the drug
(Stott et al. 1998). In 2015, Su and Klibanov investigated the possibility of forming
deep eutectic solvents with aspirin as the hydrogen bond donor (Su and Klibanov
2015). They observed that in a mixture with choline chloride (choline chloride:aspirin
2:1), the solubility of aspirin was greatly increased, and it was also more resistant to
degradation in the deep eutectic solvent. Tarate and Bansal described a deep eutectic
solvent formed between coenzyme Q and lauric acid in a 2:1 molar ratio (Tarate and
Bansal 2015). Abbott et al. also described the formation of deep eutectic solvents
between choline chloride and active pharmaceutical ingredients that could act as
hydrogen bond donors, such as salicylic acid, paracetamol, and aspirin, or between
hydrogen bond acceptors including adiphenine and ranitidine with glycerol, urea, or
aspirin (Abbott et al. 2017).
A similar approach was taken with erythritol, a sugar alcohol that is able to
inhibit the growth of biofilms and dental plaque. Lim et al. mixed this with a zwitterion and betaine and formed a complex that was stable in water and capable of
dispersing biofilms (Lim et al. 2017). Although this may not be strictly considered
as a deep eutectic solvent, they obtained similar results with a mixture of erythritol
and zinc chloride (Lim et al. 2018). The cationic complex formed was found to
disrupt the interactions within bacterial exopolysaccharides. In a similar vein, Wang
et al. created an antibacterial deep eutectic solvent using the cationic antiseptic benzalkonium chloride with acrylic acid (Wang et al. 2017). The resulting mixture
could be incorporated into a dental composite that showed good mechanical properties and biocompatibility.
In a study undertaken by Santos et al. in 2019, two molecules that could have
activity in the treatment of tuberculosis, the antibiotic ethambutol and L-arginine,
which can relieve the symptoms of tuberculosis by stimulating the immune system,
were combined with citric (Santos et al. 2019). The systems were characterized by
polarized optical microscopy, differential scanning calorimetry (DSC), and nuclear
magnetic resonance. The solubility of ethambutol in the deep eutectic solvent was
considerably higher than that in water. Some toxicity was observed toward Caco-2
cells, which seemed to be linked to the acid pH of the solvents (Santos et al. 2019).
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations
glycerol, sugars, or sugar alcohols (Jeliński et al. 2019a). They reported both
experimental results and theoretical determinations of thermodynamic parameters
using the conductor-like screening model for real solvents (COSMO-RS) protocol.
The solvent composed of choline chloride and glycerol in a 1:1 molar ratio gave the
highest solubility, and in general, equimolar proportions were the best solvents. In
the theoretical model, these mixtures were found to have the lowest enthalpy.
Therapeutic Deep Eutectic Solvents
It is possible that an active molecule can itself act as a component of a deep eutectic
solvent. As early as 1998, Stott et al. combined the nonsteroidal anti-inflammatory
drug ibuprofen with a number of terpenes, including menthol and thymol, to form
eutectic mixtures in an attempt to improve the transdermal penetration of the drug
(Stott et al. 1998). In 2015, Su and Klibanov investigated the possibility of forming
deep eutectic solvents with aspirin as the hydrogen bond donor (Su and Klibanov
2015). They observed that in a mixture with choline chloride (choline chloride:aspirin
2:1), the solubility of aspirin was greatly increased, and it was also more resistant to
degradation in the deep eutectic solvent. Tarate and Bansal described a deep eutectic
solvent formed between coenzyme Q and lauric acid in a 2:1 molar ratio (Tarate and
Bansal 2015). Abbott et al. also described the formation of deep eutectic solvents
between choline chloride and active pharmaceutical ingredients that could act as
hydrogen bond donors, such as salicylic acid, paracetamol, and aspirin, or between
hydrogen bond acceptors including adiphenine and ranitidine with glycerol, urea, or
aspirin (Abbott et al. 2017).
A similar approach was taken with erythritol, a sugar alcohol that is able to
inhibit the growth of biofilms and dental plaque. Lim et al. mixed this with a zwitterion and betaine and formed a complex that was stable in water and capable of
dispersing biofilms (Lim et al. 2017). Although this may not be strictly considered
as a deep eutectic solvent, they obtained similar results with a mixture of erythritol
and zinc chloride (Lim et al. 2018). The cationic complex formed was found to
disrupt the interactions within bacterial exopolysaccharides. In a similar vein, Wang
et al. created an antibacterial deep eutectic solvent using the cationic antiseptic benzalkonium chloride with acrylic acid (Wang et al. 2017). The resulting mixture
could be incorporated into a dental composite that showed good mechanical properties and biocompatibility.
In a study undertaken by Santos et al. in 2019, two molecules that could have
activity in the treatment of tuberculosis, the antibiotic ethambutol and L-arginine,
which can relieve the symptoms of tuberculosis by stimulating the immune system,
were combined with citric (Santos et al. 2019). The systems were characterized by
polarized optical microscopy, differential scanning calorimetry (DSC), and nuclear
magnetic resonance. The solubility of ethambutol in the deep eutectic solvent was
considerably higher than that in water. Some toxicity was observed toward Caco-2
cells, which seemed to be linked to the acid pH of the solvents (Santos et al. 2019).
2 Deep Eutectic Solvents for Innovative Pharmaceutical Formulations