Separation of praziquantel enantiomers using simulated moving bed chromatographic unit with performance designed for semipreparative applications.

Abstract

Praziquantel (PZQ) composes a regular medicine available in a tablet form to fight schistosomiasis and just half of its mass is composed by the active principle (L-PZQ), the other half, D-PZQ, is frequently associated to a strong bitter taste. Moreover, optically pure L-PZQ derivatives could be used in studies about adult and juvenile worms' resistance. Nowadays, these studies use racemic PZQ (rac-PZQ) as starting point. The D-PZQ, which would be discarded, could be racemized, coming back as feed concentration in the process. The present work aims to get L-PZQ and D-PZQ with high optical purities (more than 97%) and productivity (more than 253gkgads -1 day-1 ) towards semipreparative scale for researches involving L-PZQ, L-PZQ derivatives, and D-PZQ racemization. In order to achieve this goal, a built-in-house simulated moving bed chromatographic unit with the cellulose tris (3-chloro-4-methylphenylcarbamate) (Chiralcel OZ) as chiral stationary phase (CSP) was used to investigate different scenarios of separation according to a well-known design method called triangle theory. In all scenarios investigated, at least one of the outlet streams presented high optically purity for one of the enantiomers. Comparison with literature showed superior performance of our unit even at racemic mixture concentrations that were 10 times lower than the racemic concentrations found in literature.