The Use of Ionic Liquids for API Purifications and Its Effect on Nucleation Kinetics

摘要

The source of this interest arises from the favorable properties some Ionic Liquids can exhibit, such as low flammability, low vapor pressures, tunable physicochemical properties through appropriate ion selection, large liquidus ranges and good thermal stability. The tunability of Ionic Liquids has been one of their most widely touted and exploited benefits as solvents, as the ability to manipulate solution interactions can lead to the design of Ionic Liquids that are good solvents for chosen target compounds. This has been explored with regards to the solubility of pharmaceutical substances, and their crystallization. These approaches typically involve the use of antisolvent crystallization or a combination of liquid-liquid extraction and antisolvent crystallization to recover the target. Surprisingly, studies into the use of Ionic Liquids as solvents for the purification by crystallization of organic solids, particularly pharmaceuticals, remains relatively limited despite the industrial significance of this methodology. In order to address these concerns we have considered the use of cooling crystallization in an Ionic Liquid as a purification methodology to reduce the complexity of the resultant solution. The Ionic Liquid possesses a relatively high viscosity over a wide range of temperature and the high initial viscosity can act as kinetic barrier to both nucleation and subsequent crystallization.