Process screening studies on enantioselective extraction of (R)-Amlodipine using design of experiment (DOE)

Abstract

The enantioselective extraction of (R)-amlodipine in a biphasic recognition chiral extraction (BRCE) system combining a hydrophobic L-tartrate in organic phase and hydrophilic β-cyclodextrin (β-CD) in aqueous phase has been studied. In this work, the process screening on temperature, pH, concentration of hydroxylpropyl-β-cyclodextrin (HP-β-CD), concentration of diethyl-L-tartrate and concentration of racemic amlodipine all exert a considerable influence on the biphasic recognition process. In order to plan the procedure of experiment, Design of Experiment (DOE), that is Fractional Factorial design is used for process screening purpose. Experimental results show that concentration of L-tartrate has affect the enantiomer separation of amlodipine drug. The most significant effects were temperature, pH, concentration of HP-β-CD and concentration of racemic amlodipine. In this study, distribution coefficient of (R)-amlodipine showed the highest value at 25˚C, pH 7, 0.05 mmol/L of racemic amlodipine and 0.05 mol/L of HP-β-CD.