Partition Behavior of Drug Molecules in Cholinium-Based Ionic Liquids

Abstract

In this paper, a series of ionic liquids (ILs) contains cholinium as cations were prepared. These ILs were used as extractants to separate some model drug molecules. The partition coefficients of these drug molecules between ILs and aqueous solutions were determined. Furthermore, the influence of different extraction parameters was investigated: volume ratio, equilibrium time, pH values, temperature and ILs structure. It is shown that these ILs are highly effective materials for the extraction of drug molecules. The results imply that these ILs may have potential in drug extraction or separation as a new type of media.

Ionic-Liquid-Mediated Extraction and Separation Processes for Bioactive Compounds: Past, Present, and Future Trends

“…A and B correspond to processes where an induced precipitation with CO 2 335 and back-extraction 338,339 approaches were used to recover the pharmaceuticals, while C represents the process of purification of an intermediate of aliskiren synthesis. 343 …”

“…For this purpose, the naturally occurring cholinium cation was used for the preparation of hydrophobic ILs of increasing alkyl chain length [i.e., [N 11 n (2OH) ] + ( n = 4, 6, 8 and 10)] combined with the [NTf 2 ] − anion. 339 Four distinct drugs were investigated, namely the nonsteroidal anti-inflammatory drugs ibuprofen and indomethacin, the analgesic drug phenacetin, and the anesthetic and analgesic agent lidocaine. After the optimization of the extraction volume phase ratio and the equilibrium time, the impact of pH, the chemical structure of the ILs, and temperature upon the partitioning of the drugs was assessed.…”

“…With dependence on the drug under investigation, distinct effects were noticed: the indomethacin migration to the IL phase was significantly limited by higher pH conditions; enhanced performances were obtained for both ibuprofen and indomethacin by increasing the IL alkyl side chain length, which is in contrast to the pattern observed for lidocaine; and finally, the extraction mechanism of ibuprofen is endothermic. Finally, the authors 339 highlighted the importance of isolating the pharmaceuticals from the ILs by removing more than 65% of indomethacin through pH changes (with 0.1 mol L –1 NaOH), allowing the authors to envisage an integrated process similar to that represented in Figure 28 B.…”

“…Figure 28B shows a schematic representation of the integrated process proposed by the authors. 338 A later study by Wang and co-workers 339 focused on the development of nontoxic IL-based extraction systems. For this purpose, the naturally occurring cholinium cation was used for the preparation of hydrophobic ILs of increasing alkyl chain length [i.e., [N 11n(2OH) ] + (n = 4, 6, 8 and 10)] combined with the [NTf 2 ] − anion.…”

“…After the optimization of the extraction volume phase ratio and the equilibrium time, the impact of pH, the chemical structure of the ILs, and temperature upon the partitioning of the drugs was assessed. With dependence on the drug under investigation, distinct effects A and B correspond to processes where an induced precipitation with CO 2 335 and backextraction 338,339 approaches were used to recover the pharmaceuticals, while C represents the process of purification of an intermediate of aliskiren synthesis. 343 were noticed: the indomethacin migration to the IL phase was significantly limited by higher pH conditions; enhanced performances were obtained for both ibuprofen and indomethacin by increasing the IL alkyl side chain length, which is in contrast to the pattern observed for lidocaine; and finally, the extraction mechanism of ibuprofen is endothermic.…”