Dual-Drug Chiral Resolution: Enantiospecific Cocrystallization of (S)-Ibuprofen Using Levetiracetam

Abstract

In this work we show the feasibility of resolving a racemic drug substance with a second chiral drug. Via enantiospecific cocrystallization a dual-drug cocrystal is obtained. Such a method can be useful not only for chiral resolution but also for the parallel creation of dual-drug formulations. Here, racemic ibuprofen is resolved using levetiracetam through the formation of an enantiospecific cocrystal. Cocrystallization is utilized as a resolution tool for (in this case) (S)-ibuprofen, the active enantiomer. To find the right conditions to resolve the system, the appropriate ternary and quaternary phase diagrams were constructed. Since these diagrams are governed by thermodynamics, where the kinetic forms are prevented via seeding, the system is robust under scale-up conditions and is an interesting alternative to chiral chromatography or enantioselective synthesis for the pharmaceutical industry.