Study On Multistage Extraction Of Ketoconazole And 2-phenylpropionic Acid Enantiomers In A Cascade Of Centrifugal Contactor Separators

Chiral pharmaceutical is the forefront field in the pharmaceutical industry. Chiral separation is the most commonly used method to obtain single-enantiomer drugs. The increasing demand for single-enantiomer drugs has led to the rapidly development of a variety of chiral separation technologies. The centrifugal extraction technology was used for multistage extraction separation of ketoconazole and 2-phenylpropionic acid enantiomers with hydrophilic ?-cyclodextrin derivatives as extractant. Based on a single stage extraction model and the law of conservation of mass combining with liquid-liquid equilibrium equations, multistage enantioselective liquid-liquid extraction equilibrium models were established. The simulated program was written by Matlab package. The model was applied to simulate and optimize the multistage enantioselective liquid-liquid extraction process. Many useful multistage extraction information and optimum process parameters were obtained, which provided scientific basis for the industrial applications of extraction separation of the two chiral compounds and the design and amplification of annular centrifugal contactor separators. The main research work and corresponding results are as follows:Multistage enantioselective liquid-liquid extraction for chiral separation of KTZ enantiomers:The single-phasic recognition chiral extraction experiments were carried out at temperature of 5?. When butyl acetate was used as organic solvent and HP-?-CD was used as extractant with the concentration of 0.1 mol/L, the separation factor was 1.32. Based on a single stage extraction model, the law of mass conservation and combining with liquid-liquid equilibrium equations, a multistage enantioselective liquid-liquid extraction equilibrium model of KTZ enantiomers was established. The simulated program was written by Matlab package. Impacts of the volume flow ratios (W/O and W/F), extractant concentration, pH value of the aqueous phase as well as the number of stages on the extraction efficiency were investigated by experiments and simulations. By model prediction and optimization, an important conclusion was made for the symmetrical separation of KTZ enantiomers:The eeeq can reach up to 97% and 99% with the number of stages of 72 and 94 at temperature of 5?, W/O ratio of 3.3, W/F ratio of 40, HP-?-CD concentration of 0.1 mol/L and pH value of 8.5.Multistage enantioselective liquid-liquid extraction for chiral separation of 2-PPA enantiomers:Based on a single stage extraction model, the law of mass conservation and combining with liquid-liquid equilibrium equations, a multistage enantioselective liquid-liquid extraction equilibrium model of 2-PPA enantiomers was established. The simulated program was written by Matlab package. Impacts of the volume flow ratios (W/O and W/F), extractant concentration, pH value of the aqueous phase as well as the number of stages on the extraction efficiency were investigated by experiments and simulations. By model prediction and optimization, an important conclusion was made for the symmeyrical separation of 2-PPA enantiomers:The eeeq can reach up to 95% and 97% with the number of stages of 98 and 106 at temperature of 5?, W/O ratio of 0.55, W/F ratio of 40, HP-p-CD concentration of 0.1 mol/L and pH value of 2.5.