@article {19008,
	title = {A comparison between pure active pharmaceutical ingredients and therapeutic deep eutectic solvents: Solubility and permeability studies},
	journal = {European Journal Of Pharmaceutics And Biopharmaceutics},
	volume = {114},
	year = {2017},
	month = {2017-02-27 00:00:00},
	pages = {296-304},
	publisher = {Elsevier},
	abstract = {

THEDES, so called therapeutic deep eutectic solvents are here defined as a mixture of two components,
which at a particular molar composition become liquid at room temperature and in which one of them
is an active pharmaceutical ingredient (API). In this work, THEDES based on menthol complexed with
three different APIs, ibuprofen (ibu), BA (BA) and phenylacetic acid (PA), were prepared. The interactions
between the components that constitute the THEDES were studied by NMR, confirming that the eutectic
system is formed by H-bonds between menthol and the API. The mobility of the THEDES components was
studied by PFGSE NMR spectroscopy. It was determined that the self-diffusion of the species followed the
same behavior as observed previously for ionic liquids, in which the components migrate via jumping
between voids in the suprastructure created by punctual thermal fluctuations. The solubility and permeability
of the systems in an isotonic solution was evaluated and a comparison with the pure APIs was
established through diffusion and permeability studies carried out in a Franz cell. The solubility of the
APIs when in the THEDES system can be improved up to 12 fold, namely for the system containing
ibu. Furthermore, for this system the permeability was calculated to be 14  105 cm/s representing a
3 fold increase in comparison with the pure API. With the exception of the systems containing PA an
increase in the solubility, coupled with an increase in permeability was observed. In this work, we hence
demonstrate the efficiency of THEDES as a new formulation for the enhancement of the bioavailability of
APIs by changing the physical state of the molecules from a solid dosage to a liquid system.

}, keywords = {Diffusion coefficient, drug solubility, permeability, pharmaceutical and biomedical applications, Therapeutic deep eutectic solvents}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2017.02.003}, author = {Duarte, A. R. C. and Ferreira, A. S. D. and Barreiros, S. and Cabrita, E. and Reis, R. L. and Paiva, A.} }

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