115
Physicochemical Characterization
• Thermal characterization – this analysis is important to create a phase diagram
of the eutectic system, determining the eutectic point that corresponds to the
ratio in which a single melting point exists, corresponding to the point of the
eutectic liquid (Phaechamud et al. 2015). The degradation temperature and other
variations of temperature that could be important in these compounds also can be
observed with this analysis. In general, the thermal characterization can be performed with techniques such as differential scanning calorimetry (DSC) and
thermogravimetric analysis (TGA) that are complementary techniques that provide information about different phase transitions in different endothermic and
exothermic stages, glass transition temperature (T g ), and degradation temperature (Morrison et al. 2009; Phaechamud et al. 2015; Aroso et al. 2016).
• Spectroscopic characterization – this provides information about the structure of
the compounds and the possible interactions that exist between the different
components of the mixtures. Some examples of techniques used to observe
hydrogen bonds and intermolecular interactions are nuclear magnetic resonance
(NMR) and infrared spectroscopy (IR). The structure of THEDES was, for
example, investigated by pulsed-field gradient (PFG) NMR (Duarte et al. 2017;
Mann et al. 2019) and
1
H1
H nuclear Overhauser spectroscopy (NOESY) (Dai
et al. 2013; Aroso et al. 2016; Mann et al. 2019), which allowed the exploration
of which interactions exist in the mixture and the determination of the most probable ratios between the components. The infrared spectroscopy involves the use
of infrared radiation and is performed usually by Fourier-transform infrared
spectroscopy (FTIR) or attenuated total reflection (ATR). These techniques show
the spectral bands of known groups, and the delocalization of the shifts of these
groups could indicate the presence of hydrogen interactions between the components in the mixture (Aroso et al. 2016; Dai et al. 2013, Dai et al. 2015; Xin
et al. 2017).
• Physicochemical properties – the eutectic mixtures, usually, are liquid forms,
and for further applications, properties such as viscosity, density, polarity, and
water content are relevant for application and formulation. THEDES, generally,
are viscous fluids and their properties can be seen as an advantage or disadvantage, depending on the application in different formulations for drug delivery.
Viscosity and rheological measurements are performed using a rheometer or viscosimeter. Density can be measured using a densimeter and polarity can be
determined in a relative scale through colorimetric assays (Craveiro et al. 2016).
The water content that can be measured by Karl Fischer titration is an important
characteristic to measure, as water content values above 50% compromise the
structure and stability of the hydrogen interactions established among the components of the mixture. Further than that, it is the water content that influences
directly the viscosity, density, and polarity of the mixtures (Craveiro et al. 2016;
Dai et al. 2015).
3 Therapeutic Deep Eutectic Systems for the Enhancement of Drug Bioavailability
Physicochemical Characterization
• Thermal characterization – this analysis is important to create a phase diagram
of the eutectic system, determining the eutectic point that corresponds to the
ratio in which a single melting point exists, corresponding to the point of the
eutectic liquid (Phaechamud et al. 2015). The degradation temperature and other
variations of temperature that could be important in these compounds also can be
observed with this analysis. In general, the thermal characterization can be performed with techniques such as differential scanning calorimetry (DSC) and
thermogravimetric analysis (TGA) that are complementary techniques that provide information about different phase transitions in different endothermic and
exothermic stages, glass transition temperature (T g ), and degradation temperature (Morrison et al. 2009; Phaechamud et al. 2015; Aroso et al. 2016).
• Spectroscopic characterization – this provides information about the structure of
the compounds and the possible interactions that exist between the different
components of the mixtures. Some examples of techniques used to observe
hydrogen bonds and intermolecular interactions are nuclear magnetic resonance
(NMR) and infrared spectroscopy (IR). The structure of THEDES was, for
example, investigated by pulsed-field gradient (PFG) NMR (Duarte et al. 2017;
Mann et al. 2019) and
1
H1
H nuclear Overhauser spectroscopy (NOESY) (Dai
et al. 2013; Aroso et al. 2016; Mann et al. 2019), which allowed the exploration
of which interactions exist in the mixture and the determination of the most probable ratios between the components. The infrared spectroscopy involves the use
of infrared radiation and is performed usually by Fourier-transform infrared
spectroscopy (FTIR) or attenuated total reflection (ATR). These techniques show
the spectral bands of known groups, and the delocalization of the shifts of these
groups could indicate the presence of hydrogen interactions between the components in the mixture (Aroso et al. 2016; Dai et al. 2013, Dai et al. 2015; Xin
et al. 2017).
• Physicochemical properties – the eutectic mixtures, usually, are liquid forms,
and for further applications, properties such as viscosity, density, polarity, and
water content are relevant for application and formulation. THEDES, generally,
are viscous fluids and their properties can be seen as an advantage or disadvantage, depending on the application in different formulations for drug delivery.
Viscosity and rheological measurements are performed using a rheometer or viscosimeter. Density can be measured using a densimeter and polarity can be
determined in a relative scale through colorimetric assays (Craveiro et al. 2016).
The water content that can be measured by Karl Fischer titration is an important
characteristic to measure, as water content values above 50% compromise the
structure and stability of the hydrogen interactions established among the components of the mixture. Further than that, it is the water content that influences
directly the viscosity, density, and polarity of the mixtures (Craveiro et al. 2016;
Dai et al. 2015).
3 Therapeutic Deep Eutectic Systems for the Enhancement of Drug Bioavailability