Residence Time Distribution Characterization and Proof-of-Concept\nof a Novel Stacked 7‑Stage Continuous Crystallizer Cascade\nwith Diaphragm-Driven Slurry Transfer

Process\ndevelopers in the pharmaceutical industry lack readily\ndeployable, standardized, off-the-shelf continuous crystallizers (<100\nmL), abiding the low material requirements of early stage product\ndevelopment. This study evaluates a novel continuous tower crystallizer\n(TWC), hosting a series of seven vertically stacked mixed suspension\nmixed product removal crystallizers (MSMPRCs, 80 mL total volume)\nenabled by an innovative diaphragm driven slurry transfer, which eliminates\nknown transfer line issues in MSMPRC cascades. Residence time distribution\nmeasurements using the model compound glycine demonstrate ideal mixing\nfor both liquid (homogeneous) and solid (heterogeneous) phases (particle\n< 100 μm, slurry density < 22.8%). A comparison with the\ntank in series model reveals nonideal mixing for particles >300\nμm.\nFinally, a proof-of-concept continuous antisolvent crystallization\nof glycine demonstrates the TWC’s capability to produce high-quality\ncrystals continuously, proving its functional and robust operation.