Evaluation of mixed suspension mixed product removal crystallization processes coupled with a continuous filtration system

As the pharmaceutical industry evolves and goes through the paradigm shift from batch to continuous manufatturing, innovative processes need to be developed to replace unit operations that have historically been batch operations. This requires innovation in the continuous crystallization field of study as well as innovation in downstream processes (e.g. filtration, drying, milling, and granulation). Herein a novel and commercially available continuous filter carousel (CFC) system was assessed for its feasibility of continuous filtration while coupled with a continuous mixed suspension mixed product removal (MSMPR) crystallizer. The filtration system was assessed using two different crystallization systems (i.e. cooling and antisolvent) with significantly different kinetics and morphologies to assess the robustness of the integrated platform. With proper optimization of the various filtration parameters for the different crystallization systems a controlled state of operation was achieved in each case. The crystal product from the CFC system shows good consistency with the crystals in the slurry in the MSMPR. Moisture content and productivity of the filtration system were reported and show dependency on crystal properties. The CFC system was equipped with solvent vessels that aided the continuous filtration by acting as a wash or a clean-in-place solvent, preventing or removing filter clogging, respectively. (C) 2016 Elsevier B.V. All rights reserved.