110
reported the use of eutectic mixtures in pharmacy; however, the aim of this study
was to prevent the liquefaction and incompatibilities between the components of the
eutectic mixtures (camphor and salol), incorporating powders with absorbent characteristics as magnesium carbonate, kaolin, and magnesium oxide (Bellafiore 1953;
Prista et al. 2008). Another study performed with camphor and salol showed that
these components form a eutectic mixture with a decrease in the melting point from
43 °C of salol and 179 °C of camphor to 6 °C of the mixture salol-camphor (Prista
et al. 2008). Sekiguchi and coworkers studied eutectic mixtures and admitted that
eutectic compounds are composed by two components. Being one of them water
soluble and when exposed to gastrointestinal environment, this soluble compound
dissolves fast, keeping the insoluble part with a large superficial area and more susceptible to absorption. It was reported that for binary combinations, the eutectic
mixtures usually present a characteristic “V” type phase diagram, while the cocrystals exhibit a characteristic “W” type phase diagram (Prista et al. 2008;
Cherukuvada 2016).
Eutectic mixtures sometimes present high viscosity or cannot be formed without
the presence of water, and it was reported that adding water to a eutectic mixture in
a certain molar ratio, being water part of the mixture, could help in the preparation
of eutectic mixtures and decreases their viscosity, without compromising the system
(Dai et al. 2015). Dai and coworkers studied the effects of water incorporated in
natural deep eutectic solvents and observed that small amounts of water resulted in
mixtures with low viscosity and reduced preparation time and in general the stability and solubility are increased. Nevertheless, adding up to 50% of water to the
system could lead to the break of hydrogen bonds and dilution of the components,
making a solution and not a DES (Craveiro et al. 2016; Dai et al. 2015).
3.2.2 Advantages of Using Eutectics in Pharmacy
The use of eutectic mixtures for therapeutic applications could represent an advantage to improve formulations and avoid the drawbacks of polymorphic drugs, since
the mixtures, frequently, are in liquid form at room temperature, and could therefore
provide a better solvent for several low soluble or insoluble drugs. The intrinsic
characteristics of eutectic mixtures such as low melting point, liquid form, 100%
yield, high solvent stability, and low toxicity confer to these systems an opportunity
for the search of mixtures that could improve the drug bioavailability and pharmacokinetics, by adding characteristics to the API that lead to an efficient absorption,
high biocompatibility, high solubility and permeability, and low toxicity. These
parameters are essential for determining the bioavailability of an API, and the use of
eutectic mixtures could enable to have new formulations or improved formulations
without modifying the API (Álvarez and Zhang 2019).
The pharmaceutical industry has designed mostly crystalline APIs for formulation; however, many of these drugs fail in testing, due to issues with delivery mechanisms, like dissolution, transport, bioavailability, and polymorphism that could
F. Santos and A. R. C. Duarte
reported the use of eutectic mixtures in pharmacy; however, the aim of this study
was to prevent the liquefaction and incompatibilities between the components of the
eutectic mixtures (camphor and salol), incorporating powders with absorbent characteristics as magnesium carbonate, kaolin, and magnesium oxide (Bellafiore 1953;
Prista et al. 2008). Another study performed with camphor and salol showed that
these components form a eutectic mixture with a decrease in the melting point from
43 °C of salol and 179 °C of camphor to 6 °C of the mixture salol-camphor (Prista
et al. 2008). Sekiguchi and coworkers studied eutectic mixtures and admitted that
eutectic compounds are composed by two components. Being one of them water
soluble and when exposed to gastrointestinal environment, this soluble compound
dissolves fast, keeping the insoluble part with a large superficial area and more susceptible to absorption. It was reported that for binary combinations, the eutectic
mixtures usually present a characteristic “V” type phase diagram, while the cocrystals exhibit a characteristic “W” type phase diagram (Prista et al. 2008;
Cherukuvada 2016).
Eutectic mixtures sometimes present high viscosity or cannot be formed without
the presence of water, and it was reported that adding water to a eutectic mixture in
a certain molar ratio, being water part of the mixture, could help in the preparation
of eutectic mixtures and decreases their viscosity, without compromising the system
(Dai et al. 2015). Dai and coworkers studied the effects of water incorporated in
natural deep eutectic solvents and observed that small amounts of water resulted in
mixtures with low viscosity and reduced preparation time and in general the stability and solubility are increased. Nevertheless, adding up to 50% of water to the
system could lead to the break of hydrogen bonds and dilution of the components,
making a solution and not a DES (Craveiro et al. 2016; Dai et al. 2015).
3.2.2 Advantages of Using Eutectics in Pharmacy
The use of eutectic mixtures for therapeutic applications could represent an advantage to improve formulations and avoid the drawbacks of polymorphic drugs, since
the mixtures, frequently, are in liquid form at room temperature, and could therefore
provide a better solvent for several low soluble or insoluble drugs. The intrinsic
characteristics of eutectic mixtures such as low melting point, liquid form, 100%
yield, high solvent stability, and low toxicity confer to these systems an opportunity
for the search of mixtures that could improve the drug bioavailability and pharmacokinetics, by adding characteristics to the API that lead to an efficient absorption,
high biocompatibility, high solubility and permeability, and low toxicity. These
parameters are essential for determining the bioavailability of an API, and the use of
eutectic mixtures could enable to have new formulations or improved formulations
without modifying the API (Álvarez and Zhang 2019).
The pharmaceutical industry has designed mostly crystalline APIs for formulation; however, many of these drugs fail in testing, due to issues with delivery mechanisms, like dissolution, transport, bioavailability, and polymorphism that could
F. Santos and A. R. C. Duarte