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3.3 Applications of Therapeutic Deep Eutectic Systems
in Research and Industry
The therapeutic deep eutectic systems represent an attractive and sustainable method
to explore an infinite number of possible combinations with different components
that incorporate or dissolve a drug. For industry and research, it is a very interesting
area that provides the possibility of improving the characteristics of the APIs (solubility and permeability, for example). However, other properties could be enhanced
depending on the compounds that are part of the mixture. Incorporating natural
compounds with very low toxicity can, for instance, reduce the toxicity of a drug,
while the incorporation of an antioxidant can tune the antioxidant properties of the
API (Zainal-Abidin et al. 2019; Álvarez and Zhang 2019).
In the last decade, the interest and knowledge for providing solutions for old
biomedical and pharmaceutical problems has increased. The objective remains to
find alternative and safe biomaterials, active compounds, and routes of administration of “old” drugs that improve their characteristics, turn them less toxic, and facilitate the therapeutics (Aroso et al. 2016).
3.3.1 Therapeutic Deep Eutectic Systems for Improvement
of the Bioavailability of Drugs
The most common approach to form eutectic mixtures and use them in pharmacy is
trying to incorporate one or more APIs as components of the eutectic mixture.
Bonain discovered a eutectic mixture for topical anesthesia that includes cocaine
hydrochloride, phenol, or menthol to form a homogeneous liquid at room temperature. Nevertheless, it was observed that cocaine has toxic effects and phenol has
caustic properties (Gala et al. 2014). Evers and coworkers, in 1981, reported the use
of a eutectic mixture of lidocaine and prilocaine (1:1) in an oil-in-water emulsion to
increase the analgesic effect through the skin. With this mixture, they described an
increase of the concentration of local anesthetic in the emulsion of approximately
20% to 80% of lidocaine-prilocaine, maintaining the total concentration of the local
anesthetic low (5%) (Buckley and Benfield (1993); Evers et al. (1985); Lowrie et al.
1989). The transdermal permeation enhancement of this cream (trade name EMLA)
is possible through the combination of the components that decreases the melting
point of the mixture to approximately 22 °C, while the compounds individually
have low permeation through the skin, due to their melting points higher than the
body temperature (37 °C) (Cherukuvada and Nangia (2014); Yin and Jiang (2018);
Woolfson et al. 2000). It was though observed that prilocaine has high tendency to
cause methemoglobinemia, and this discovery led Gala and coworkers to study
other eutectic mixtures for lidocaine, such as lidocaine-tetracaine and lidocainecamphor (Gala et al. 2014).
3 Therapeutic Deep Eutectic Systems for the Enhancement of Drug Bioavailability
3.3 Applications of Therapeutic Deep Eutectic Systems
in Research and Industry
The therapeutic deep eutectic systems represent an attractive and sustainable method
to explore an infinite number of possible combinations with different components
that incorporate or dissolve a drug. For industry and research, it is a very interesting
area that provides the possibility of improving the characteristics of the APIs (solubility and permeability, for example). However, other properties could be enhanced
depending on the compounds that are part of the mixture. Incorporating natural
compounds with very low toxicity can, for instance, reduce the toxicity of a drug,
while the incorporation of an antioxidant can tune the antioxidant properties of the
API (Zainal-Abidin et al. 2019; Álvarez and Zhang 2019).
In the last decade, the interest and knowledge for providing solutions for old
biomedical and pharmaceutical problems has increased. The objective remains to
find alternative and safe biomaterials, active compounds, and routes of administration of “old” drugs that improve their characteristics, turn them less toxic, and facilitate the therapeutics (Aroso et al. 2016).
3.3.1 Therapeutic Deep Eutectic Systems for Improvement
of the Bioavailability of Drugs
The most common approach to form eutectic mixtures and use them in pharmacy is
trying to incorporate one or more APIs as components of the eutectic mixture.
Bonain discovered a eutectic mixture for topical anesthesia that includes cocaine
hydrochloride, phenol, or menthol to form a homogeneous liquid at room temperature. Nevertheless, it was observed that cocaine has toxic effects and phenol has
caustic properties (Gala et al. 2014). Evers and coworkers, in 1981, reported the use
of a eutectic mixture of lidocaine and prilocaine (1:1) in an oil-in-water emulsion to
increase the analgesic effect through the skin. With this mixture, they described an
increase of the concentration of local anesthetic in the emulsion of approximately
20% to 80% of lidocaine-prilocaine, maintaining the total concentration of the local
anesthetic low (5%) (Buckley and Benfield (1993); Evers et al. (1985); Lowrie et al.
1989). The transdermal permeation enhancement of this cream (trade name EMLA)
is possible through the combination of the components that decreases the melting
point of the mixture to approximately 22 °C, while the compounds individually
have low permeation through the skin, due to their melting points higher than the
body temperature (37 °C) (Cherukuvada and Nangia (2014); Yin and Jiang (2018);
Woolfson et al. 2000). It was though observed that prilocaine has high tendency to
cause methemoglobinemia, and this discovery led Gala and coworkers to study
other eutectic mixtures for lidocaine, such as lidocaine-tetracaine and lidocainecamphor (Gala et al. 2014).
3 Therapeutic Deep Eutectic Systems for the Enhancement of Drug Bioavailability