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

被引：0

作者：

Aprile, Giovanni ^{[1
,2
,3
]}

Pandit, Ajinkya V. ^{[1
]}

Albertazzi, Jody ^{[4
]}

Vetter, Thomas ^{[3
]}

Viano, Robert ^{[5
]}

Milani, Lorenzo ^{[5
]}

Adamo, Andrea ^{[5
]}

Myerson, Allan S. ^{[1
]}

Stelzer, Torsten ^{[1
,6
,7
]}

机构：

[1] MIT, Dept Chem Engn, Cambridge, MA 02139 USA

[2] Tech Univ Denmark DTU, Dept Chem & Biochem Engn, DK-2800 Kongens Lyngby, Denmark

[3] H Lundbeck A S, DK-2500 Valby, Denmark

[4] Politecn Milan, Dept Chem Mat & Chem Engn G Natta, I-20133 Milan, Italy

[5] Zaiput Flow Technol, Waltham, MA 02451 USA

[6] Univ Puerto Rico, Dept Pharmaceut Sci, San Juan, PR 00936 USA

[7] Univ Puerto Rico, Crystallizat Design Inst, Mol Sci Res Ctr, San Juan, PR 00926 USA

来源：

INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH | 2024年 / 63卷 / 42期

基金：

美国国家科学基金会;

关键词：

PRODUCT-REMOVAL CRYSTALLIZATION; CONTINUOUS-FLOW; MIXED-SUSPENSION; PROCESS INTENSIFICATION; BATCH CRYSTALLIZATION; MSMPR CRYSTALLIZATION; TECHNOLOGY-TRANSFER; AXIAL-DISPERSION; PROCESS WINDOWS; SCALE-UP;

D O I：

10.1021/acs.iecr.4c02153

中图分类号：

TQ [化学工业];

学科分类号：

0817 ;

摘要：

Process developers in the pharmaceutical industry lack readily deployable, standardized, off-the-shelf continuous crystallizers (<100 mL), abiding the low material requirements of early stage product development. This study evaluates a novel continuous tower crystallizer (TWC), hosting a series of seven vertically stacked mixed suspension mixed product removal crystallizers (MSMPRCs, 80 mL total volume) enabled by an innovative diaphragm driven slurry transfer, which eliminates known transfer line issues in MSMPRC cascades. Residence time distribution measurements using the model compound glycine demonstrate ideal mixing for both liquid (homogeneous) and solid (heterogeneous) phases (particle < 100 mu m, slurry density < 22.8%). A comparison with the tank in series model reveals nonideal mixing for particles >300 mu m. Finally, a proof-of-concept continuous antisolvent crystallization of glycine demonstrates the TWC's capability to produce high-quality crystals continuously, proving its functional and robust operation.

引用

页码：18199 / 18211

页数：13