106
processes and research methods (Anastas and Eghbali 2010; Welton 2015). In this
chapter, the focus will be on the application and development of deep eutectic systems in pharmaceutical field and their importance for the improvement of the API
properties, namely, the increase of their bioavailability.
3.2 History of Green Solvents and Evolution Until
Therapeutic Deep Eutectic Systems
The concept of green solvents was introduced by John Warner and Paul Anastas, in
1998, when they listed the 12 principles of green chemistry. One of the green chemistry principles assumes that the use of solvents should be as an auxiliary substances,
in the synthesis and preparation processes, and emphases that they should be made
unnecessary whenever possible, and if used they should be innocuous (Anastas and
Warner 1998; Warner et al. 2004). The sustainability of a process or a product is,
hence, a result of the complex interaction between the product or process implemented and environment, technology, and economic factors (Welton 2015).
In the last decades, the research on green or safer solvents, recognized as environmentally benign, has been growing exponentially. However, it is necessary to
consider the source and synthesis of the solvent, its properties, and the disposal. A
variety of compounds have been considered as green solvents such as water, supercritical and subcritical fluids, ionic liquids, solvents derived from biomass, and
more recently deep eutectic systems (Bubalo et al. 2015; Francisco et al. 2013;
Hayyan et al. 2015; Welton 2015). Strategies for the development of green solvents
that lead to the substitution of petroleum-based solvents by solvents from renewable
resources have been explored. Furthermore, the substitution of hazardous solvents
by solvents that present better environmental, health, and safety properties is also a
topic of intense research (Bubalo et al. 2015; Welton 2015).
Ionic liquids (ILs) appeared for the first time in 1914, described by Paul Walden
in the synthesis of ethylammonium nitrate in a reaction that involves nitric acid
(Domínguez de María and Maugeri 2011; Kudlak et al. 2015). An IL is defined as
an organic salt composed by ions that result in a single salt with a melting point
below 100 °C; some examples of cations and anions that are commonly used for the
synthesis of ionic liquids are presented in Fig. 3.1. In the last years, they have been
frequently used and investigated as green solvents (Ferraz et al. 2011; Hough et al.
2007; Liu et al. 2018a, b; Pena-Pereira and Namieśnik 2014). One of the applications of ionic liquids which was foreseen as a major breakthrough in industry was
to replace volatile organic compounds (VOCs), presenting a safer alternative and
exhibiting high solvency and a negligible vapor pressure (Brennecke and Maginn
2001; Heckenbach et al. 2016; Hough and Rogers 2007).
Ionic liquids have been developed in sequent generations. The first generation of
ILs appeared in the 1960s and describes compounds that are designed in accordance
with desired physical properties, such as hydrophobicity, viscosity, density, thermal
F. Santos and A. R. C. Duarte
processes and research methods (Anastas and Eghbali 2010; Welton 2015). In this
chapter, the focus will be on the application and development of deep eutectic systems in pharmaceutical field and their importance for the improvement of the API
properties, namely, the increase of their bioavailability.
3.2 History of Green Solvents and Evolution Until
Therapeutic Deep Eutectic Systems
The concept of green solvents was introduced by John Warner and Paul Anastas, in
1998, when they listed the 12 principles of green chemistry. One of the green chemistry principles assumes that the use of solvents should be as an auxiliary substances,
in the synthesis and preparation processes, and emphases that they should be made
unnecessary whenever possible, and if used they should be innocuous (Anastas and
Warner 1998; Warner et al. 2004). The sustainability of a process or a product is,
hence, a result of the complex interaction between the product or process implemented and environment, technology, and economic factors (Welton 2015).
In the last decades, the research on green or safer solvents, recognized as environmentally benign, has been growing exponentially. However, it is necessary to
consider the source and synthesis of the solvent, its properties, and the disposal. A
variety of compounds have been considered as green solvents such as water, supercritical and subcritical fluids, ionic liquids, solvents derived from biomass, and
more recently deep eutectic systems (Bubalo et al. 2015; Francisco et al. 2013;
Hayyan et al. 2015; Welton 2015). Strategies for the development of green solvents
that lead to the substitution of petroleum-based solvents by solvents from renewable
resources have been explored. Furthermore, the substitution of hazardous solvents
by solvents that present better environmental, health, and safety properties is also a
topic of intense research (Bubalo et al. 2015; Welton 2015).
Ionic liquids (ILs) appeared for the first time in 1914, described by Paul Walden
in the synthesis of ethylammonium nitrate in a reaction that involves nitric acid
(Domínguez de María and Maugeri 2011; Kudlak et al. 2015). An IL is defined as
an organic salt composed by ions that result in a single salt with a melting point
below 100 °C; some examples of cations and anions that are commonly used for the
synthesis of ionic liquids are presented in Fig. 3.1. In the last years, they have been
frequently used and investigated as green solvents (Ferraz et al. 2011; Hough et al.
2007; Liu et al. 2018a, b; Pena-Pereira and Namieśnik 2014). One of the applications of ionic liquids which was foreseen as a major breakthrough in industry was
to replace volatile organic compounds (VOCs), presenting a safer alternative and
exhibiting high solvency and a negligible vapor pressure (Brennecke and Maginn
2001; Heckenbach et al. 2016; Hough and Rogers 2007).
Ionic liquids have been developed in sequent generations. The first generation of
ILs appeared in the 1960s and describes compounds that are designed in accordance
with desired physical properties, such as hydrophobicity, viscosity, density, thermal
F. Santos and A. R. C. Duarte