Determination Of Competative Adsorption Isotherms Of Amlodipine Enantiomers And The Chromatography Separation By Simulated Moving Bed

Amlodipine is mainly used in the clinical treatment of hypertension and angina pectoris.Its molecular structure contains one chiral carbon atom,so there is one pair of enantiomers.S-amlodipine is an enantiomer monomer that plays a major pharmacodynamic role in amlodipine mixture,which is thousands of times more potent in treating blood pressure than dextrin.Therefore,the resolution of amlodipine enantiomers is important for people's health by using drugs to avoid side effects.Chromatographic separation is an important method in chiral separation.The resolution of the preparative chromatography is mainly nonlinear competitive adsorption,since the separation between the enantiomeric monomers is carried out under a high concentration of solvent.In the preparation process of simulated moving bed(SMB)chromatography,it is necessary to select the correct adsorption model to provide accurate model parameters and improve the optimal value of the separation process parameter selection to achieve separation optimization.This paper uses the inverse method to determine the adsorption isotherm model.Amlodipine enantiomer drug system was selected,and a certain high concentration of amlodipine solution was prepared at 10°C.The overload and outflow curve was determined by high performance liquid chromatography on a chiral column Chiralpak OD-H column.The overload and outflow curves were fitted using a computer program to obtain adsorption isotherm models and model parameters for amlodipine at this temperature.The column model selects the equilibrium diffusion model to reflect the transient process of amlodipine in the column.When using computer programs to fit experimental data,you need to find an optimal initial value and then optimize the model parameters using the Levenberg-Marquardt algorithm(LMA).If the initial value of the parameter is artificially selected,it is very time consuming and very difficult.However,the non-dominated genetic algorithm(NSGA-II)is used to determine the adsorption isotherm model parameters,but the optimal initial value can be found among the numerous parameters.The combination of the two algorithms can accurately and quickly fit the parameters of the adsorption isotherm model.The fitting of the experimental data and the verification of the model parameters by computer program show that the 5-parameter Bi-Langmuir model has the best fit.Using the determined model and model parameters,it is applied to the "triangle theory" in order to obtain the optimal operating conditions for the simulated moving bed during the separation process.The simulation experiment of the simulated moving bed established the separation conditions of the amlodipine enantiomer.The yield and purity of levamlodipine can reach 100% and 98%.The effects of simulated moving bed operating conditions Ts,QD,QR,and QE on the yield and purity of levamlodipine were analyzed.