Dynamic cross-flow filtration: enhanced continuous small-scale solid-liquid separation.

In a previous study, a small-scale dynamic filtration device (SFD) was analyzed and the basic mechanisms governing the filtration process were characterized. The present work aims at improving the device's performance in terms of actual production. Various operation modes were tested in order to increase permeate flow and concentration factors (CF), while maintaining a fully continuous production mode. Both, a vacuum-enhanced and a pulsating operation mode, proved to be superior to the currently implemented open-operation mode. For example, for lactose, an increase of the CF could be achieved from 1.7 in open mode to 7.6 in pulsating operation mode. The investigated operation strategy enables process control systems to rapidly react to fluctuating feeds that may occur due to changes in upstream manufacturing steps. As a result, not only filtration performance in terms of permeate rate but also process flexibility can be significantly increased. Overall, vacuum-enhanced operation was shown to be most promising for integration into an industrial environment. The option to elevate achievable concentration factors, ease of flow monitoring as well as the ability to react to changes in the feed conditions allow for effective and efficient continuous small-scale filtration.

Continuous Processing of Active Pharmaceutical Ingredients Suspensions via Dynamic Cross-Flow Filtration.

Over the last years, continuous manufacturing has created significant interest in the pharmaceutical industry. Continuous filtration at low flow rates and high solid loadings poses, however, a significant challenge. A commercially available, continuously operating, dynamic cross-flow filtration device (CFF) is tested and characterized. It is shown that the CFF is a highly suitable technology for continuous filtration. For all tested model active pharmaceutical ingredients, a material-specific strictly linear relationship between feed and permeate rate is identified. Moreover, for each tested substance, a constant concentration factor is reached. A one-parameter model based on a linear equation is suitable to fully describe the CFF filtration performance. This rather unexpected finding and the concentration polarization layer buildup is analyzed and a basic model to describe the observed filtration behavior is developed.