RECOVERY OF (-)-PRAZIQUANTEL FROM RACEMIC MIXTURES BY CONTINUOUS CHROMATOGRAPHY AND CRYSTALLIZATION

Enantiomerically pure (-)-praziquantel, an anthelmintic drug, is resolved by coupling a continuous chromatographic process and a multi-stage crystallisation. The partial separation of praziquantel racemic mixture is first achieved by a simulated countercurrent chromatographic (SCC) process. The chiral stationary phase used is microcrystalline cellulose triacetate and the mobile phase is methanol. The SCC system consists of eight identical chromatographic columns (445 mm x 12.5 mm ID) connected in series. At steady state, the raffinate and extract streams contain 97.5% (-)-praziquantel and 85.0% (+)-praziquantel, respectively. The raffinate stream from the chromatographic process is concentrated and allowed to crystallise at -15 degrees C. The crystallisation process is optimised with the aid of the solubility phase diagram determined in a previous study. The recovery of the (-)-praziquantel crystals is maximised by performing a four-stage crystallisation. By coupling these two processes, about 11.7 g of the enantiomerically pure (-)-praziquantel can be obtained per day at an overall recovery of about 80% with the present set-up.