Evaluation of Solubility, Physicochemical Properties, and Cytotoxicity of Naproxen-Based Ionic Liquids
Yimei Tang, Kuan Yang, Siyu Zhao, Qingqing Chen, Lan Qin, Bei Qin
Abstract
High Resolution Image Download MS PowerPoint Slide To solve the problems associated with poorly water-soluble nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen-based ionic liquids (ILs) containing naproxen as an active pharmaceutical ingredient (API) anion were prepared with benzalkonium (tetradecyldimethylbenzyl ammonium), choline, and 1-octyl-3-methylimidazole as the cation. The structures and thermal properties were analyzed. Through the conductivity method, the solubility at 25 and 37 °C and the critical micelle concentration (CMC) at 25 °C were determined in water and ethanol. The octanol–water partition coefficients ( K ow ) at 25 °C were measured with the shake-flask method. The cytotoxicity was evaluated with the MTT method. The results showed that the conversion of naproxen into the API-ILs increased the API’s solubility in water by more than 850 times compared with the original API, and the thermostability was satisfactory with a lower glass transition temperature ( t g ). Moreover, the variation trends of solubility, hydrophilicity, and K ow were consistent with the different structures of naproxen-based ILs, except for benzalkonium naproxen. The CMC (10 –5 –10 –6 M) in water and ethanol demonstrated that the naproxen-based ILs were surface activite ILs. The IC 50 values exhibited the low cytotoxicity of the naproxen-based ILs, which was better than 100 μM. The results provide essential information and a research basis for future topical and transdermal administration and oral administration of naproxen-based ILs.