(63af) Purification of Ibuprofen Enantiomers By a New Technique Combining Distillation and Crystallization

Stripping crystallization (SC) is a new separation technique which combines distillation and crystallization. Basically, SC is operated at a triple-point condition, in which the liquid is simultaneously vaporized and crystallized due to the three-phase equilibrium. In essence, the process is continued until the liquid phase is completely eliminated and only the pure solid crystals remain in the feed. Thus, crystal washing is not required since only pure solid crystals remain in the feed and no impurities are adhered on the crystal surfaces at the end of SC. In the previous research, SC has been successfully applied to separate p-xylene from the mixed xylenes by Shiau et al. (2005, 2008, 2013).

Ibuprofen, also called 2-(isobutylphenyl)-propionic acid, is a non-steroidal anti-inflammatory drug widely used to treat headaches and minor pains. Although it is known that S-ibuprofen is responsible for the anti-inflammatory effects while R-ibuprofen might cause some long-term side effects, ibuprofen is still sold as a racemic mixture in the market due to the complexity involved in the separation of enantiomers. A thermodynamic model is developed in this work to simulate the three-phase equilibrium conditions during the SC operation. The experiments show that 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.

References:

1.  Shiau, L. D.*, Wen, C. C. and Lin, B. S. “Separation and purification of p-xylene from the mixture of m-xylene and p-xylene by distillative freezing”, Ind. Eng. Chem. Res, 44(7), p2258-2265, 2005.

2.  Shiau, L. D.*, Wen, C. C. and Lin, B. S. “Separation of p-xylene from the multicomponent xylene system by stripping crystallization”, AIChE Journal, 54(1), p337-342, 2008.

3. Shiau, L. D.*; Liu, K. F. ”Investigations into the effects of the cooling rate on stripping crystallization”, Ind. Eng. Chem. Res, 52, p1716-1722, 2013.