Akbarzadeh Gondoghdi Parisa, Khorsandi Mohammad, Mokhtarpour Masumeh, Shekaari Hemayat, Hamishehkar Hamed
Department of Physical Chemistry, University of Tabriz, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
BMC Chem. 2024 Jun 3;18(1):109. doi: 10.1186/s13065-024-01212-4.
Recently, there is a particular interest to utilize protic ionic liquids (PILs) in drug solubility. This study is exploring the effect of three protic ionic liquids (PILs) based on 2-hydroxyethylammonium carboxylate [2-hydroxyethylammonium acetate (MEAA), 2-hydroxyethylammonium lactate (MEAL), and 2-hydroxyethylammonium propionate (MEAP)] on the solubility of the very poorly soluble drug in water, indomethacin (IMC). The shake flask method was used to measure the experimental solubility of IMC at the different temperatures range (298.15-313.15) K. The results demonstrate significantly enhancment the solubility of IMC in PILs compared to pure water, with an approximate increase of 200 times. The experimental solubility data have been correlated using the empirical models which showed the performance as the order: Modified Apelblat-Jouyban-Acree > Van't Hoff-Jouyban-Acree > Modified Apelblat equations and also the performance for the Wilson model indicated as the order (absolute relative deviation): 2-hydroxyethylammonium acetate (3.030) > 2-hydroxyethylammonium propionate (3.239) > 2-hydroxyethylammonium lactate (7.665). Then the thermodynamic dissolution properties were obtained by usage of Gibbs and Van't Hoff equations to investigate the thermodynamic behavior of the IMC in the aqueous solution PILs. Eventually, the cytotoxicity of the co-solvents (PILs) under study was evaluated using a standard MTT assay. The results showed that the cell viability percentage increased in the following order: MEAA < MEAP < MEAL. These findings indicated that these PILs had low to moderate toxicity. It is noteworthy that the functional groups of the anions were not the only determinant factor of the cytotoxicity. Other factors encompassing concentration, exposure time, and cell line characteristics also had significant effects.
最近，利用质子离子液体（PILs）来提高药物溶解度受到了特别关注。本研究探讨了三种基于2-羟乙基铵羧酸盐的质子离子液体[2-羟乙基铵乙酸盐（MEAA）、2-羟乙基铵乳酸盐（MEAL）和2-羟乙基铵丙酸盐（MEAP）]对水溶解度极差的药物吲哚美辛（IMC）溶解度的影响。采用摇瓶法测定了IMC在不同温度范围（298.15 - 313.15）K下的实验溶解度。结果表明，与纯水相比，IMC在PILs中的溶解度显著提高，大约增加了200倍。实验溶解度数据已使用经验模型进行关联，结果表明各模型性能顺序为：修正的Apelblat-Jouyban-Acree模型＞Van't Hoff-Jouyban-Acree模型＞修正的Apelblat方程，并且Wilson模型的性能（绝对相对偏差）顺序为：2-羟乙基铵乙酸盐（3.030）＞2-羟乙基铵丙酸盐（3.239）＞2-羟乙基铵乳酸盐（7.665）。然后通过吉布斯方程和范特霍夫方程获得热力学溶解性质，以研究IMC在PILs水溶液中的热力学行为。最终，使用标准MTT法评估了所研究的共溶剂（PILs）的细胞毒性。结果表明，细胞活力百分比按以下顺序增加：MEAA＜MEAP＜MEAL。这些发现表明这些PILs具有低至中等毒性。值得注意的是，阴离子的官能团不是细胞毒性的唯一决定因素。其他因素，包括浓度、暴露时间和细胞系特征也有显著影响。
