The use of cooling crystallization in an ionic liquid system for the purification of pharmaceuticals
File(s)
Author(s)
Weber, CC
Kulkarni, SA
Kunov-Kruse, AJ
Rogers, RD
Myerson, AS
Type
Journal Article
Abstract
The application of ionic liquids (ILs) as solvents is frequently discussed in the context of their tunability, with the potential to tailor the solvent system uniquely to the process being investigated. Instead, here we study the potential for a single IL, 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C2C1Im][NTf2]), to be used for the cooling crystallization of a wide range of active pharmaceutical ingredients (APIs). [C2C1Im][NTf2] was selected on the basis of its thermal stability, low reactivity and miscibility with solvents of moderate polarity which suggests that it is miscible with liquids of comparable polarities to many API molecules. The overwhelming majority of APIs tested were soluble at >50 wt% within [C2C1Im][NTf2] at elevated temperatures despite relatively poor solubility at room temperature. This dramatic effect was ascribed to the miscibility of most of the molten APIs with the IL. The solubility curves for nine APIs were measured which established the potential use of this IL as a crystallization solvent. Finally, cooling crystallizations were conducted using acetaminophen containing common impurities as models. The cooling crystallizations within [C2C1Im][NTf2] were found to produce acetaminophen in similar or greater purity with substantially improved yields relative to a number of control cooling and antisolvent crystallizations.
Date Issued
2015-09-16
Date Acceptance
2015-08-12
Citation
Crystal Growth & Design, 2015, 15 (10), pp.4946-4951
ISSN
1528-7483
Publisher
American Chemical Society
Start Page
4946
End Page
4951
Journal / Book Title
Crystal Growth & Design
Volume
15
Issue
10
Copyright Statement
© 2015 American Chemical Society
Subjects
Inorganic & Nuclear Chemistry
Physical Chemistry (Incl. Structural)
Materials Engineering
Inorganic Chemistry
Publication Status
Published