Simulation for Chiral Separation of Bupivacaine by SMB

초록

It is well known that chirality plays an important role in areas such as pharmaceuticals due to the different activity and toxicological profiles of each enantiomer in human body. Therefore, various separation methods for the enantiomeric determination of drug have been developed. The chromatographic methods using chiral stationary phases (CSPs) have been the most widely applied in the last few years, so the resulting chiral high-performance liquid chromatography (HPLC) is being a standard technique. But, it is a non-continuous process and has high solvent consumption and low productivity. To overcome this problem, simulated moving bed (SMB) technology has been utilized to pharmaceuticals chemicals, particularly to enantiomer separation. In this work, S-bupivacanine with the pharmacological activity of epidural anaesthesia was isolated and separated from R-bupivacanine by SMB chromatography. Nonlinear isotherm was suggested from the single column experiment and the mass transfer coefficient was obtained from an empirical equation. The parameters of a in competitive Langmuir adsorption equation empirically determined by PIM (pulsed input method) for R and S-bupibacaine were 6.20, 8.79 mg/ml, respectively, while those of b were 0.364, 0.922 ml/mg, respectively. These equilibrium and kinetic parameters were used by a commercially available simulator to find the optimum operating condition for resolving the two racemic mixtures. The SMB system was composed of eight columns(1×10cm) packed Kromasil　 CHI-TBB and was configured 2-2-2-2. The mobile phase composition was n-hexane/IPA/acetic acid/triethylamine, 99/1/0.2/0.05 (vol. fraction). To determine the optimum operating conditions, SMB simulator, Aspen Chromatography was used. It was experimentally confirmed that based on these experimental conditions, the separation of bupivacaine enantiomers was successfully performed with the purity of more than 98% by SMB