104
investigation in pharmaceutical field and in drug development have been very
focused on the improvement of the characteristics of existing drugs.
The major points of this review focus on the development of deep eutectic systems for therapeutic applications, namely, therapeutic deep eutectic systems
(THEDES), that emerged as a good alternative to overcome the drawbacks of some
of the existing drugs, mainly in terms of bioavailability. These systems are presented as alternative solvents that could be prepared with an active pharmaceutical
ingredient incorporated in the eutectic mixture or could act as a delivery vehicle,
dissolving the drug in it. Recent developments on these systems show that THEDES
could also be impregnated in matrices for the development of medical devices or
controlled drug delivery systems, for example, using supercritical CO 2 .
Keywords Deep eutectic systems · Pharmacy · Controlled drug delivery ·
Alternative solvents · Green chemistry · Bioavailability
Abbreviations
THEDES
Therapeutic deep eutectic systems
API
Active pharmaceutical ingredient
ILs
Ionic liquids
VOCs
Volatile organic compounds
DES
Deep eutectic solvent
LTTM
Low transition temperature mixtures
NADES
Natural deep eutectic solvents
DSC
Differential scanning calorimetry
TGA
Thermogravimetric analysis
T g
Glass transition temperature
NMR
Nuclear magnetic resonance
IR
Infrared spectroscopy
PFG-NMR
Pulsed-field gradient of nuclear magnetic resonance
NOESY
2D nuclear Overhauser spectroscopy
FTIR
Fourier-transform infrared spectroscopy
ATR
Attenuated total reflection
BCS
Biopharmaceutics classification system
FDA
Food and Drug Administration
MTS
3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4sulfophenyl)-2H-tetrazolium (dye for cell viability assay)
MTT
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (dye
for cell viability assay)
IC 50
Half-maximal inhibitory concentration
POM
Polarized optical microscopy
CAGE
Deep eutectic solvent choline and geranate
F. Santos and A. R. C. Duarte