Modeling multiple chemical equilibrium for reactive extraction of naproxen enantiomers with HP-β-CD as hydrophilic selector

Abstract

Reactive extraction is an emerging technology for large-scale continuous resolution of drug enantiomers. The enantioselective extraction of R,S-naproxen by hydrophilic HP--CD in 1,2-dichloroethane was studied at 5 °C. The experimental data were described by a reactive extraction model with a homogeneous aqueous phase reaction of R,S-naproxen with HP--CD which couples a complete description of chemical equilibria in aqueous phase with the overall phase equilibria of the system. Important parameters of this model were determined experimentally. The physical distribution coefficients for molecular and ionic NAP were 0.041 and 1.730, respectively. Here we show that the efficiency of extraction depends strongly on two process variables including pH and HP--CD concentration. The model predictions are compared graphically with the results of previous experiments and there is a good agreement between each other. By the use of modeling and experiment, an optimized extraction condition with pH of 2.5 and HP--CD concentration of 0.1 mol/L was obtained with high enantioselectivity (  ) of 1.59 and performance factor (pf) of 0.049. The model gives a good means of predicting enantiomers partitioning over a range of experimental conditions.

Enantioseparation of Three Non-Steroidal Anti-Inflammatory Agents on Chiral Stationary Phase by HPLC

“…A variety of chiral stationary phase (CSP) methods have been proposed for the chiral separation of Naproxen, ketoprofen, such as CHIRAL-CEL OD, (+) 18-C-6-TA, (R,R)-Whelk-O1, etc. [16][17][18]. However, there is no literature search about the chiral separation of Naproxen, Etodolac on CHI-DMB CSPs and none of them was enantioseparated on (R,R)-DNB-DPEDA by HPLC.…”