Study On Kinetics Of Enantioselective Extraction Of Drug Enantiomers

This paper reports on kinetics of reactive extraction of hydrophobic drugenantiomers from the organic phase to the aqueous phase by hydrophilic-CDsolution. The model of kinetics of reactive extraction was established and obtain theoptimal extraction conditions. The main contents and results can be summarized asfollows:In ibuprofen （IBU） extraction system, the theory of extraction accompanied bychemical reactions has been used to obtain the intrinsic kinetics of extraction of IBUenantiomers by hydroxypropyl-β-cyclodextrin （HP--CD）. The effects of processparameters including agitation speed, interfacial area, initial concentration IBUenantiomers, initial concentration of extractant and pH value of aqueous phase, oninitial extraction rate were separately studied. The reactions are first order in IBU andsecond order in HP--CD with the forward rate constants of7.21×10^-4mol-2m⁶s^-1for S-IBU and4.58×10^-4mol-2m⁶s^-1for R-IBU, respectively. By comparison of theexperimental values with the model predictions, it is found that the model predictionsare in good agreement with the experiment.In pranoprofen （PRA） extraction system, the theory of extraction accompaniedby a chemical reaction has been used to obtain the kinetics. The reactions betweenmethyl-β-cyclodextrin （Me--CD） and PRA enantiomers in a stirred cell fall inRegime3, extraction accompanied by a fast chemical reaction in the diffusion film.The effects of process parameters including agitation speed, interfacial area, initialconcentration of PRA enantiomers, initial concentration of extractant and pH value ofaqueous phase, on initial extraction rate were separately studied.The reactions are firstorder with respect to PRA and second order with respect to Me--CD. The forwardrate constants are2.82×10^-4m⁶/（mol²s） for S-PRA and3.53×10^-4m⁶/（mol²s） forR-PRA, respectively. By comparison of the experimental values with the modelpredictions, it is found that the model predictions are in good agreement with theexperiment.In oxybutynin （OBN） extraction system, the kinetic experiments were carried out ina modified Lewis cell, in which hydrophobic OBN enantiomers was initiallydissolved in the organic solvent and extracted into the aqueous phase byhydroxypropyl-β-cyclodextrin （HP--CD）. The effects of process parameters including agitation speed, interfacial area, initial concentration of OBN enantiomers,initial concentration of extractant and pH value of aqueous phase, on initial extractionrate were separately studied. Results show that the extraction reaction kinetics is fast.The reactions are first order with respect to OBN and second order with respect toHP--CD. The forward rate constants are6.12×10-5m⁶·mol-2·s^-1for R-OBN and1.13×10^-4m⁶·mol-2·s^-1for S-OBN, respectively. By comparison of the experimentalvalues with the model predictions, it is found that the model predictions are in goodagreement with the experiment.