Solubility Studies of Cyclosporine Using Ionic Liquids

Paula Berton; Manish Kumar Mishra; Hemant Choudhary; Allan S Myerson; Robin D Rogers

doi:10.1021/acsomega.9b00603

Solubility Studies of Cyclosporine Using Ionic Liquids

ACS Omega. 2019 May 1;4(5):7938-7943. doi: 10.1021/acsomega.9b00603. eCollection 2019 May 31.

Authors

Paula Berton¹, Manish Kumar Mishra², Hemant Choudhary², Allan S Myerson³, Robin D Rogers²

Affiliations

¹ Chemical and Petroleum Engineering Department, University of Calgary, 2500 University Drive NW, Calgary AB T2N 1N4, Canada.
² College of Arts & Sciences, The University of Alabama, 712 Capstone Drive, Tuscaloosa, Alabama 35401, United States.
³ Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

Abstract

Six ionic liquids (ILs) were selected based on their chemical and physical properties to study the solubility of cyclosporine A. Of these, cyclosporine exhibited higher room temperature solubility in 1-ethyl-3-methylimidazolium acetate ([C₂mim][OAc]) than in acetone, an effective molecular solvent used to solubilize and purify cyclosporine. The solubility of cyclosporine in the ILs dramatically increased at higher temperatures, a critical factor that cannot be varied in a wide range with low boiling molecular solvents. The differences in solubility were explored for cyclosporine purification. Cyclosporine was purified up to ∼93% with n-butylammonium acetate ([C₄NH₃][OAc]) and could be further purified to 95% using an IL/organic solvent biphasic system. After purification, cyclosporine was recovered as an amorphous solid using the ILs.