(725h) Leveraging Mother Liquor Viscosity in Non-Ideal Systems to Optimize Filtration Time

In pharmaceutical processing, filtration is a key unit operation in the production of active pharmaceutical ingredients (API) and API intermediates. Long filtration times can greatly impact cycle time and filtration issues can be more complex when using a centrifuge. To prepare for scale up into a centrifuge, understanding the parameters which can influence the filtration performance (i.e. flux, compressibility) is key to predicting cycle times. Many factors contribute to filtration performance, but one factor that is often overlooked is viscosity of the mother liquor. N-Methylpyrrolidone (NMP) is a common polar process solvent, however NMP/ water and NMP/ alcohol systems are non-ideal and result in very viscous mixtures that can negatively impact filtration time. A case study will be presented where the filtration of a pharmaceutical intermediate from an NMP/water system was improved through consideration of mixture viscosity. The development included an assessment of solvent selection and crystal property modifications. Filtration flux measurements and process modeling were used to identify the benefit of a ternary solvent system to reduce supernatant viscosity. This resulted in an improved filtration flux while maintaining product yield and quality.