Optimization Of Extraction Conditions For Rifamycin

Rifamycin SV and rifamycin S are important intermediates for the synthesis of anti-tuberculosis drugs.The traditional solvent extraction process is often used for the extraction of rifamycin SV and rifamycin S.The preparation of rifamycin and its sodium salt in industry usually goes through a series of steps such as fermentation,filtration,oxidation,extraction,demulsification,washing,crystallization and drying.The distinct emulsification will occur when the fermentation broth is extracted by organic solvent.After the ester layer is separated,demulsifier is added to separate the raffinate.This will lead to demulsification time is too long,so that a large number of antibiotics are entrained in the emulsion,resulting in a decline in product yield and purity.In addition,when the extraction pH value is between 2 and 3,rifamycin is unstable under strong acidic conditions,which is easy to decompose in the long static separation process,resulting in a decrease in the final yield.In order to solve this problem,the extraction pH value was increased and a multi-stage rapid extraction process was adopted.Rifamycin extraction was studied in chlorine-free environment by using centrifugal extractor instead of glass-lined stirrer in production.The effects of extraction pH,extraction temperature,water ester ratio and initial solution concentration on the partition coefficients and extraction yields of rifamycin S and SV under single stage extraction were investigated.At the same time,rifamycin SV was extracted by multi-stage countercurrent extraction.The results of multi-stage countercurrent extraction were simulated and calculated by using the relationship between the concentration of water phase and the distribution coefficient in single-stage equilibrium and the material conservation equation in multi-stage countercurrent operation.The results show that:(1)The distribution coefficients of rifamycin S and SV have the same trend under different conditions,and are positively correlated with extraction temperature and water ester,negatively correlated with extraction pH and initial solution concentration.(2)The extraction yields of rifamycin S and SV decreased with the increase of pH.The extraction yields of rifamycin S and SV were 71.69%and 83.25%respectively at pH=4.2.Temperature is directly proportional to the extraction rate,and the highest extraction rate is 61.21%and 67.37%respectively at 45 ℃.The change of water ester ratio had little effect on the extraction yield,and the extraction rate of the two was basically stable.The extraction yields of rifamycin S and SV reached the maximum at the initial solution concentration of 2004.09 μ/mL.49.36%and 55.62%respectively.(3)The higher the extraction series,the higher the yield of rifamycin SV.When pH=4.2,T=45 ℃ and VA/VO=1,the extraction rates of th e second and third stages were 98.50%and 99.80%respectively,and the corresponding experimental values were 96.82%and 98.07%respectively,which were much higher than those of the single stage.In this paper,centrifugal extractor was used to optimize the traditional solvent extraction process conditions.Rifamycin could also obtain higher extraction yield after three-stage countercurrent extraction at higher pH value.The results of this study are expected to provide guidance for industrial production of rifamycin S and SV.