Improvement of New Dianionic Ionic Liquids vs Monoanionic in Solubility of Poorly Water-Soluble Drugs
Improvement of New Dianionic Ionic Liquids vs Monoanionic in Solubility of Poorly Water-Soluble Drugs
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DOI：
10.1016/j.xphs.2021.01.014
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发表时间：
2021-05-14
影响因子：
3.8
通讯作者：
Reis, Patricia M.
中科院分区：
文献类型：
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作者：
Agostinho, Daniela A. S.;Jesus, Ana R.;Reis, Patricia M.
合成并表征了一种以膦酸根阴离子和铵盐阳离子为基础的新型离子液体。它们被用作赋形剂，以增加两种口服药物吡罗昔康和布洛芬的水溶性，这两种药物微溶于水。与纯水相比，布洛芬的溶解度增加了300倍，IL在水中仅占0.25摩尔%。有趣的是，这是用毒性较低的双阴离子液体[N4 1 2OH 2OH]2 [C2H5PO3]实现的，其IC50为120 mM（z0.25 mol%）。另一方面，对于相同的双阴离子液体，在相同的离子液体百分比下，吡罗昔康显示出480倍的增加。相反，对于单阴离子型离子液体，效果不是那么明显，并且在0.3摩尔%的IL的存在下仅获得10倍。这些离子液体的存在下，药物的亲脂性（logP）下降。测定了这些IL的细胞毒性特征，并且它们未显示出对健康成纤维细胞的显著影响。布洛芬和吡罗昔康的细胞毒性也被确定，和细胞活力几乎没有改变时，离子液体在1 mM的口服药物的存在下。(c)2021年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
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 (z0.25 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. (c) 2021 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.