Evaluation of Solubility, Physicochemical Properties, and Cytotoxicity of Naproxen-Based Ionic Liquids

Abstract

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.

Effect of feeding astaxanthin with different E/Z‐isomer ratios on astaxanthin accumulation in Pacific white shrimp Litopenaeus vannamei

“…[ 19,20,29 ] Recent studies have demonstrated that astaxanthin Z ‐isomers not only have higher bioavailability but also exhibit greater biological activities (e.g., antielastase, anti‐inflammatory, and antiaging activities) than the all‐ E ‐isomer. [ 8–10,30 ] Thus, boiling enhanced the nutritional value of L. vannamei .…”

Ionic Liquids: New Forms of Active Pharmaceutical Ingredients with Unique, Tunable Properties

“…The ILs characterized by this method include, for example, tetracycline docusate, 169 and cholinium, 1-octyl-3methylimidazolium, and benzalkonium naproxenates. 201…”

“…These samples are subsequently centrifuged, and concentrations of the compounds are accessed in both phases by the same techniques described above. The ILs characterized by this method include, for example, tetracycline docusate, and cholinium, 1-octyl-3-methyl­imidazolium, and benzalkonium naproxenates …”

“…Thus, in the synthesis of cholinium naproxenate the authors reported the presence of 3−5% water/volatiles, according to TGA, but conducted water solubility and octanol−water partition coefficient studies anyway. 201 Nuclear magnetic resonance (NMR) is employed for structural confirmation of composed products. 287 For the determination of unreacted starting materials (i.e., proving the intended stoichiometry), conducting 1 H NMR (quantities greater than 1 mol %) with proper integration is vital.…”

“…For API-ILs, thermogravimetric analysis (TGA) is often used, but this technique is not sensitive enough (<1%). Thus, in the synthesis of cholinium naproxenate the authors reported the presence of 3–5% water/volatiles, according to TGA, but conducted water solubility and octanol–water partition coefficient studies anyway …”