Precipitation/Nanofiltration Hybrid Process to Purify Esomeprazole from Phosphate-Containing Bioreaction Solution

The purification of high-value-added pharmaceutical products from the byproducts is among the toughest challenges during practical processes. During the production of esomeprazole, the residual phosphate buffer and cosolvent in the bioreaction solution hinder the molecular separation and purification of the esomeprazole after the biosynthesis process. This work creatively combines precipitation and nanofiltration processes to realize the high-efficiency separation between phosphate and esomeprazole. PO₄^3- and HPO₄^2- with molecular sizes similar to that of esomeprazole and multiple valences were effectively converted to KCl via a precipitation process with <3% loss of esomeprazole. Thus, the KCl with a smaller molecular size and lower valence can be separated by the following multistage NF process, which operated under a pH of 11 with a 5% methanol cosolvent existing. The hybrid process refined the esomeprazole to a concentration nearly twice that of the raw bioreaction's aqueous solution and meanwhile removed nearly 100% of phosphates and over 60% of kalium ions. This hybrid process demonstrates a novel and effective approach for refining high-value-added products from byproducts under mild operation conditions, which is very promising for application in the pharmaceutical industry.