Chiral purification of S-ibuprofen from ibuprofen enantiomers by stripping crystallization

Abstract

A new technology, stripping crystallization (SC), is introduced in this work for chiral purification of S-ibuprofen from ibuprofen enantiomers. Basically, SC combines distillation and crystallization operated at reduced temperature and pressure for the liquid mixture feed to produce pure S-ibuprofen crystals and mixture vapors by maintaining a series of the three-phase equilibrium conditions based on the variations of the liquid composition. SC is continued until liquid is nearly eliminated. The final product only consists of S-ibuprofen crystals as all the vapors produced are removed from the system. A thermodynamic model is developed to simulate the three-phase equilibrium during the SC operation and to direct the batch SC experiments. The experiments show that, when SC is operated from 50°C and 290Pa to 37°C and 148Pa, seeding with ultrasound mixing or magnetic stirring can be efficiently employed to purify S-ibuprofen from ibuprofen enantiomers. The experimental results, including the final enantiomeric purity and recovery ratio of S-ibuprofen, are consistent with the simulation results predicted by the model.