Nanofiltration-based diafiltration process for solvent exchange in pharmaceutical manufacturing

Jignesh P. Sheth, Yingjie Qin, Kamalesh K. Sirkar, Basil C. Baltzis

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Athermal solvent exchange from one organic synthesis step to the next step is highly desirable in bulk pharmaceutical manufacturing due to the thermally labile nature of the active intermediates. Diafiltration (DF) was employed using methanol as the solvent needed in the next synthesis step to drastically reduce the concentration of ethyl acetate used as the solvent in the previous synthesis step. Ethyl acetate was reduced to the level of a low concentration impurity in methanol by both batch and continuous DF using solvent resistant nanofiltration membranes MPF-50 and MPF-60; the latter has a high rejection of around 96% for the solute, erythromycin, representing an active intermediate. Nanofiltration-based diafiltration for exchanging the solvent methanol for ethyl acetate was demonstrated. The membrane rejection of the solute needs to be higher. Membrane compaction has to be considered in the design of the process for both membranes.

Original languageEnglish (US)
Pages (from-to)251-261
Number of pages11
JournalJournal of Membrane Science
Issue number2
StatePublished - Jan 31 2003

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • General Materials Science
  • Physical and Theoretical Chemistry
  • Filtration and Separation


  • Diafiltration
  • Nanofiltration
  • Solvent exchange
  • Solvent stable membranes


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