121
with pure drug. In spite of eutectic mixtures are most of the times in a liquid form,
they can be used directly for processing and manufacturing of solid forms and at the
same time improve the characteristics of the drugs (Patel et al. 2019; Álvarez and
Zhang 2019).
Several papers in the literature report the use of supercritical fluid technology as
a versatile technology for the preparation of different formulations. Using different
particle formation techniques such as rapid expansion of supercritical solutions
(RESS), particle from gas saturated solution (PGSS), supercritical antisolvent
(SAS), or GAS for coprecipitation of the drug and the polymer, it is possible to
produce particles, for example, encapsulating drug in a polymer matrix (Guney and
Akgerman 2002; Reverchon et al. 2009). Silva et al. explored the loading of gauzes
with a eutectic blend of lauric acid:myristic acid by supercritical CO 2 . With these
novel approaches, it was possible to obtain homogeneous eutectic blends and
improve their antibacterial properties, which could be explained by the increase of
the hydrophobicity of the blend formulated that may improve their ability to interact
with the membrane of the bacteria (Silva et al. 2019a, b, c). In an attempt to find and
effective therapy for tuberculosis treatment, Roda and coworkers investigated for
the first time the encapsulation of THEDES with anti-tuberculosis drugs, as a component of the mixture, through PGSS and evaluate the influence of different water
ratios present on the mixtures on the PGSS process (Roda et al. 2020).
Supercritical carbon dioxide technology can be used for the incorporation of a
drug in a polymeric matrix rendering a controlled release systems basis on a slight
plasticization of the polymeric particles that fused together and produce a 3D structure. Silva et al. reported the possibility of using the THEDES choline
chloride:ascorbic acid and solubilized dexamethasone in the eutectic mixture, which
was then impregnated in a polymeric matrix by supercritical CO 2 . This system
could be important in studies of bone tissue engineering, because its components
could assist osteogenic differentiation from stem cells (Barros et al. 2017; Silva
et al. 2018).
Aroso and coworkers studied the development of controlled drug delivery systems of anti-inflammatory drugs, namely, using the THEDES menthol:ibuprofen
and a biodegradable polymer, composed by a blend of starch, and obtained threedimensional porous materials with supercritical fluid sintering (Aroso et al. 2015;
Roda et al. 2019). In this work, the release of ibuprofen from THEDES form has
shown significant differences, being the ibuprofen dissolved in THEDES released
much faster than API itself.
The impregnation of THEDES with supercritical CO 2 is still a research area that
remains relatively unexplored, particularly due to the lack of measurements on the
binary systems of THEDES and CO 2 . The vapor liquid equilibria (VLE) experiments are relevant to optimize the operating conditions for impregnation, such that
the amount of THEDES impregnated is within its therapeutic window. However,
Barros et al. explore the impregnation of a THEDES system (menthol:ibuprofen) in
alginate sponges that were prepared by freeze-drying, supercritical CO 2 was used
for the impregnation of THEDES, and the solubility of these binary systems
(THEDES + CO 2 ) was studied (Barros et al. 2017).
3 Therapeutic Deep Eutectic Systems for the Enhancement of Drug Bioavailability
with pure drug. In spite of eutectic mixtures are most of the times in a liquid form,
they can be used directly for processing and manufacturing of solid forms and at the
same time improve the characteristics of the drugs (Patel et al. 2019; Álvarez and
Zhang 2019).
Several papers in the literature report the use of supercritical fluid technology as
a versatile technology for the preparation of different formulations. Using different
particle formation techniques such as rapid expansion of supercritical solutions
(RESS), particle from gas saturated solution (PGSS), supercritical antisolvent
(SAS), or GAS for coprecipitation of the drug and the polymer, it is possible to
produce particles, for example, encapsulating drug in a polymer matrix (Guney and
Akgerman 2002; Reverchon et al. 2009). Silva et al. explored the loading of gauzes
with a eutectic blend of lauric acid:myristic acid by supercritical CO 2 . With these
novel approaches, it was possible to obtain homogeneous eutectic blends and
improve their antibacterial properties, which could be explained by the increase of
the hydrophobicity of the blend formulated that may improve their ability to interact
with the membrane of the bacteria (Silva et al. 2019a, b, c). In an attempt to find and
effective therapy for tuberculosis treatment, Roda and coworkers investigated for
the first time the encapsulation of THEDES with anti-tuberculosis drugs, as a component of the mixture, through PGSS and evaluate the influence of different water
ratios present on the mixtures on the PGSS process (Roda et al. 2020).
Supercritical carbon dioxide technology can be used for the incorporation of a
drug in a polymeric matrix rendering a controlled release systems basis on a slight
plasticization of the polymeric particles that fused together and produce a 3D structure. Silva et al. reported the possibility of using the THEDES choline
chloride:ascorbic acid and solubilized dexamethasone in the eutectic mixture, which
was then impregnated in a polymeric matrix by supercritical CO 2 . This system
could be important in studies of bone tissue engineering, because its components
could assist osteogenic differentiation from stem cells (Barros et al. 2017; Silva
et al. 2018).
Aroso and coworkers studied the development of controlled drug delivery systems of anti-inflammatory drugs, namely, using the THEDES menthol:ibuprofen
and a biodegradable polymer, composed by a blend of starch, and obtained threedimensional porous materials with supercritical fluid sintering (Aroso et al. 2015;
Roda et al. 2019). In this work, the release of ibuprofen from THEDES form has
shown significant differences, being the ibuprofen dissolved in THEDES released
much faster than API itself.
The impregnation of THEDES with supercritical CO 2 is still a research area that
remains relatively unexplored, particularly due to the lack of measurements on the
binary systems of THEDES and CO 2 . The vapor liquid equilibria (VLE) experiments are relevant to optimize the operating conditions for impregnation, such that
the amount of THEDES impregnated is within its therapeutic window. However,
Barros et al. explore the impregnation of a THEDES system (menthol:ibuprofen) in
alginate sponges that were prepared by freeze-drying, supercritical CO 2 was used
for the impregnation of THEDES, and the solubility of these binary systems
(THEDES + CO 2 ) was studied (Barros et al. 2017).
3 Therapeutic Deep Eutectic Systems for the Enhancement of Drug Bioavailability