112
API, since their features could offer solubility and dissolution enhancement of
poorly soluble drugs (Aroso et al. 2016; Cherukuvada and Nangia 2014).
Goldberg and coworkers studied eutectic mixtures with urea and paracetamol,
concluding that the mixture leads to a significant increase in the solubility and gastrointestinal absorption of paracetamol (Prista et al. 2008; Goldberg et al. 1966).
Later on, Dichi and coworkers reinvestigate eutectic mixtures formed with
paracetamol, acetylsalicylic acid, and caffeine and observed eutectic and metatectic
points close to each other in the mixture paracetamol-caffeine (138.6 and 139.5 °C),
and then they determined the eutectic composition of the mixture by Tamman’s triangle for each phase diagram (Dichi et al. 2018).
In another study, Stott and coworkers observed that deep eutectic systems could
be formed with the incorporation of an API in the DES, creating, hence, the possibility of develop controlled drug delivery devices, and improving the characteristics
of the APIs themselves (Aroso et al. 2016; Stott et al. 1998), also showed an
enhancement of solubility of drugs in different eutectic mixtures with choline chloride (Morrison et al. 2009).
Goud and colleagues investigated the formation of eutectic mixtures with curcumin that is an active compound and a hydrophobic polyphenol that could present
diverse therapeutic activities like anti-inflammatory, antioxidant, anticancer and
potentially used for Alzheimer’s disease (Goud et al. 2012). Curcumin has problems
of solubility and, consequently, bioavailability, and because of that, many strategies
have been used for enhancing the stability and bioavailability of curcumin, such as
use of nanoparticles and micelles, polymorphs, cocrystals, and then eutectic compositions with nicotinamide, ferulic acid, hydroquinone, p-hydroxybenzoic acid, and
L-tartaric acid. These eutectic compositions with therapeutic components have
shown an enhancement of the solubility and were prepared by mechanochemical
grinding to provide stabilized mixtures by weak and short-range interactions (Goud
et al. 2012).
3.2.3 Different Methods for Preparation of Therapeutic Deep
Eutectic Systems
In terms of preparation of therapeutic deep eutectic systems (THEDES), there are a
few methods described in the literature for the preparation of these mixtures
(Meneses et al. 2019). The most commonly used procedure is to mix the components at a certain molar ratio, stirring and heating (with temperatures that usually
vary between 40 and 80 °C), until a clear liquid is formed. The mixture could also
be prepared in a mortar and a pestle, placed in stirring or vortexing. The temperature
used is always dependent on the components present in the mixture, since sugars,
for example, are not stable at high temperatures for long periods of time (Aroso
et al. 2016; García-Argüelles et al. 2013; Serrano et al. 2012; Meneses et al. 2019).
Another method described for the preparation of eutectic systems is through
F. Santos and A. R. C. Duarte
API, since their features could offer solubility and dissolution enhancement of
poorly soluble drugs (Aroso et al. 2016; Cherukuvada and Nangia 2014).
Goldberg and coworkers studied eutectic mixtures with urea and paracetamol,
concluding that the mixture leads to a significant increase in the solubility and gastrointestinal absorption of paracetamol (Prista et al. 2008; Goldberg et al. 1966).
Later on, Dichi and coworkers reinvestigate eutectic mixtures formed with
paracetamol, acetylsalicylic acid, and caffeine and observed eutectic and metatectic
points close to each other in the mixture paracetamol-caffeine (138.6 and 139.5 °C),
and then they determined the eutectic composition of the mixture by Tamman’s triangle for each phase diagram (Dichi et al. 2018).
In another study, Stott and coworkers observed that deep eutectic systems could
be formed with the incorporation of an API in the DES, creating, hence, the possibility of develop controlled drug delivery devices, and improving the characteristics
of the APIs themselves (Aroso et al. 2016; Stott et al. 1998), also showed an
enhancement of solubility of drugs in different eutectic mixtures with choline chloride (Morrison et al. 2009).
Goud and colleagues investigated the formation of eutectic mixtures with curcumin that is an active compound and a hydrophobic polyphenol that could present
diverse therapeutic activities like anti-inflammatory, antioxidant, anticancer and
potentially used for Alzheimer’s disease (Goud et al. 2012). Curcumin has problems
of solubility and, consequently, bioavailability, and because of that, many strategies
have been used for enhancing the stability and bioavailability of curcumin, such as
use of nanoparticles and micelles, polymorphs, cocrystals, and then eutectic compositions with nicotinamide, ferulic acid, hydroquinone, p-hydroxybenzoic acid, and
L-tartaric acid. These eutectic compositions with therapeutic components have
shown an enhancement of the solubility and were prepared by mechanochemical
grinding to provide stabilized mixtures by weak and short-range interactions (Goud
et al. 2012).
3.2.3 Different Methods for Preparation of Therapeutic Deep
Eutectic Systems
In terms of preparation of therapeutic deep eutectic systems (THEDES), there are a
few methods described in the literature for the preparation of these mixtures
(Meneses et al. 2019). The most commonly used procedure is to mix the components at a certain molar ratio, stirring and heating (with temperatures that usually
vary between 40 and 80 °C), until a clear liquid is formed. The mixture could also
be prepared in a mortar and a pestle, placed in stirring or vortexing. The temperature
used is always dependent on the components present in the mixture, since sugars,
for example, are not stable at high temperatures for long periods of time (Aroso
et al. 2016; García-Argüelles et al. 2013; Serrano et al. 2012; Meneses et al. 2019).
Another method described for the preparation of eutectic systems is through
F. Santos and A. R. C. Duarte