|
In order to improve the level of mycophenolic acid extraction process,considering the physical and chemical properties of mycophenolic acid andthe fermentation broth, the broth pH is adjusted to 10-11, and the activeingredients of mycophenolic acid are released into the filtrate. Then acombination of different filtering experiments, such as re-use of frame,ceramic membrane, ultrafiltration membrane, nanofiltration membrane,have been optimized for pilot programs. Finally 0.2um ceramic membrane,20,000 MWCO KJ hollow fiber membrane and DK nanofiltrationmembrane roll are screened out.After ceramic membrane filtration for effective solid-liquid separation,the crystallization of macromolecules such as proteins and pigments largeamounts of impurities are effectively removed by ultrafiltration filtrate, andhigher quality crystal products are obtained. Then through furthernanofiltration concentration, crystallization, refining, drying, the finishedproduct is obtained. Through validation batches, the purity is more than99% and single impurity is less than 0.2% by HPLC, so the progress is infull compliance with pharmaceutical standards.With the membrane technology the filtering yield is more than 85%,and crystallization coarse product content, appearance, colour and lustre are improved obviously, as the content is increased from 40% to 85%. Theextraction total yield is reached to 65-70%. The input organic solvent isreduced by 70%, as well as the wastage of organic solvent is decreased by80%. The method shows great applicable value in the age of policyadvocating conserving the resource, green production, and sustainabledevelopment.
|