LAQV, Requimte, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, 2829-516, Portugal.
LAQV, Requimte, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, 2829-516, Portugal.
J Pharm Sci. 2021 Jun;110(6):2489-2500. doi: 10.1016/j.xphs.2021.01.014. Epub 2021 Jan 21.
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 [N] [CHPO], which presents an IC 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.
新型基于二阴离子膦酸根阴离子和铵阳离子的离子液体被制备并进行了表征。它们被用作辅料来增加两种口服药物（吡罗昔康和布洛芬）的水溶性，这两种药物在水中的溶解度都较低。与纯水相比，当水中仅含有 0.25 mol%的 IL 时，布洛芬的溶解度增加了 300 倍。有趣的是，这是通过毒性较低的二阴离子离子液体 [N] [CHPO] 实现的，其 IC 为 120 mM（≈0.25 mol%）。另一方面，对于相同的二阴离子离子液体，吡罗昔康的溶解度增加了 480 倍，且 IL 百分比相同。相比之下，对于单阴离子离子液体，效果并不那么明显，仅在存在 0.3 mol%的 IL 时，才获得了 10 倍的增加。药物的亲脂性（logP）在存在这些 IL 的情况下降低了。这些 IL 的细胞毒性特征被确定，它们对健康成纤维细胞没有显著影响。布洛芬和吡罗昔康的细胞毒性也被确定，当离子液体存在 1 mM 的口服药物时，细胞活力几乎没有变化。
