TY - JOUR
T1 - Improvement of New Dianionic Ionic Liquids vs Monoanionic in Solubility of Poorly Water-Soluble Drugs
AU - Agostinho, Daniela A. S.
AU - Jesus, Ana R.
AU - Silva, Ana B. P.
AU - Esperança, José M. S. S.
AU - Paiva, Alexandre
AU - Duarte, Ana R. C.
AU - Reis, Patrícia M.
N1 - info:eu-repo/grantAgreement/FCT/3599-PPCDT/127013/PT#
The authors thank Fundacao para a Ciencia e Tecnologia, FCT/MCTES (Portugal) for financial support through an Investigator contract (IF/00621/2015P.
M. Reis) and (IF/01146/2015A. Paiva) , and through projects IF/00621/2015 and CryoDES (PTDC/EQU-EQU/29851/2017) . This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme, under grant agreement No ERC2016CoG 725034. This work was also partially supported by the Associate Laboratory for Green ChemistryLAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020)
PY - 2021/6
Y1 - 2021/6
N2 - New ionic liquids (ILs) based on dianionic phosphonate anions and ammonium cations were prepared and characterized. They were used as excipients to increase the water solubility of two oral drugs, piroxicam and ibuprofen, that are slightly soluble in water. An increment in solubility of 300-fold was achieved for ibuprofen when compared with pure water, with only 0.25 mol% of IL in water. Interestingly, this was achieved with the less toxic dianionic ionic liquid [N4 1 2OH 2OH]2 [C2H5PO3], which presents an IC50 of 120 mM (≈0.25 mol%). On the other hand, piroxicam showed an increase of 480-fold for the same dianionic ionic liquid, with the same ionic liquid percentage. In contrast, for monoanionic ionic liquids, the effect was not so pronounced, and only a 10-fold was obtained, in the presence of 0.3 mol% of IL. The lipophilicity (logP) of drugs decreased in the presence of these ILs. Cytotoxicity profile of these ILs was determined and they did not show a significant impact towards healthy fibroblasts. The cytotoxicity of ibuprofen and piroxicam was also determined, and cellular viability almost did not change when ionic liquid was in the presence of 1 mM of oral drug.
AB - New ionic liquids (ILs) based on dianionic phosphonate anions and ammonium cations were prepared and characterized. They were used as excipients to increase the water solubility of two oral drugs, piroxicam and ibuprofen, that are slightly soluble in water. An increment in solubility of 300-fold was achieved for ibuprofen when compared with pure water, with only 0.25 mol% of IL in water. Interestingly, this was achieved with the less toxic dianionic ionic liquid [N4 1 2OH 2OH]2 [C2H5PO3], which presents an IC50 of 120 mM (≈0.25 mol%). On the other hand, piroxicam showed an increase of 480-fold for the same dianionic ionic liquid, with the same ionic liquid percentage. In contrast, for monoanionic ionic liquids, the effect was not so pronounced, and only a 10-fold was obtained, in the presence of 0.3 mol% of IL. The lipophilicity (logP) of drugs decreased in the presence of these ILs. Cytotoxicity profile of these ILs was determined and they did not show a significant impact towards healthy fibroblasts. The cytotoxicity of ibuprofen and piroxicam was also determined, and cellular viability almost did not change when ionic liquid was in the presence of 1 mM of oral drug.
KW - Bioavailability
KW - Cytotoxicity
KW - Dianionic ionic liquids
KW - Drug delivery
KW - Ionic liquids
UR - http://www.scopus.com/inward/record.url?scp=85100241570&partnerID=8YFLogxK
U2 - 10.1016/j.xphs.2021.01.014
DO - 10.1016/j.xphs.2021.01.014
M3 - Article
C2 - 33484731
AN - SCOPUS:85100241570
SN - 0022-3549
VL - 110
SP - 2489
EP - 2500
JO - Journal Of Pharmaceutical Sciences
JF - Journal Of Pharmaceutical Sciences
IS - 6
ER -