Towards achieving a flattop crystal size distribution by continuous seeding and controlled growth

Mo Jiang; Min Hao Wong; Zhilong Zhu; Jieqian Zhang; Lifang Zhou; Ke Wang; Ashlee N. Ford Versypt; Tong Si; Lisa M. Hasenberg; Yao En Li; Richard D. Braatz

doi:10.1016/j.ces.2011.12.033

Towards achieving a flattop crystal size distribution by continuous seeding and controlled growth

Mo Jiang
, Min Hao Wong
, Zhilong Zhu
, Jieqian Zhang
, Lifang Zhou
, Ke Wang
, Ashlee N. Ford Versypt
, Tong Si
, Lisa M. Hasenberg
, Yao En Li
, Richard D. Braatz

Department of Chemical and Biological Engineering

University of Illinois at Urbana-Champaign
Massachusetts Institute of Technology
Abbott Laboratories

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

Abstract

A semi-continuous crystallizer configuration that combines continuous seeding using a dual impinging jet with growth rate control in a stirred tank was experimentally demonstrated for the manufacture of l-asparagine monohydrate (LAM) crystals with the objective of obtaining a target flattop size distribution. The dual impinging jets combined hot and cold saturated solutions to generate highly uniform 20-μm crystals that were further grown to a desired size in the stirred tank with suppressed nucleation that was instrumented with attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and focused beam reflectance measurement (FBRM). The construction of calibration models and the measurement of solubility and metastable limit were obtained by an automated system that followed preset supersaturation profiles using feedback control. The experiments confirm that greatly enhanced control of the crystal size distribution can be achieved using continuous seeding.

Original language	English
Pages (from-to)	2-9
Number of pages	8
Journal	Chemical Engineering Science
Volume	77
DOIs	https://doi.org/10.1016/j.ces.2011.12.033
State	Published - Jul 30 2012

Keywords

Concentration feedback control
Crystallization
Crystallizer design
Dual impinging jets
Pharmaceuticals
Process intensification

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10.1016/j.ces.2011.12.033

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title = "Towards achieving a flattop crystal size distribution by continuous seeding and controlled growth",

abstract = "A semi-continuous crystallizer configuration that combines continuous seeding using a dual impinging jet with growth rate control in a stirred tank was experimentally demonstrated for the manufacture of l-asparagine monohydrate (LAM) crystals with the objective of obtaining a target flattop size distribution. The dual impinging jets combined hot and cold saturated solutions to generate highly uniform 20-μm crystals that were further grown to a desired size in the stirred tank with suppressed nucleation that was instrumented with attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and focused beam reflectance measurement (FBRM). The construction of calibration models and the measurement of solubility and metastable limit were obtained by an automated system that followed preset supersaturation profiles using feedback control. The experiments confirm that greatly enhanced control of the crystal size distribution can be achieved using continuous seeding.",

keywords = "Concentration feedback control, Crystallization, Crystallizer design, Dual impinging jets, Pharmaceuticals, Process intensification",

author = "Mo Jiang and Wong, \{Min Hao\} and Zhilong Zhu and Jieqian Zhang and Lifang Zhou and Ke Wang and \{Ford Versypt\}, \{Ashlee N.\} and Tong Si and Hasenberg, \{Lisa M.\} and Li, \{Yao En\} and Braatz, \{Richard D.\}",

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doi = "10.1016/j.ces.2011.12.033",

language = "English",

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journal = "Chemical Engineering Science",

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AU - Jiang, Mo

AU - Wong, Min Hao

AU - Zhu, Zhilong

AU - Zhang, Jieqian

AU - Zhou, Lifang

AU - Wang, Ke

AU - Ford Versypt, Ashlee N.

AU - Si, Tong

AU - Hasenberg, Lisa M.

AU - Li, Yao En

AU - Braatz, Richard D.

PY - 2012/7/30

Y1 - 2012/7/30

N2 - A semi-continuous crystallizer configuration that combines continuous seeding using a dual impinging jet with growth rate control in a stirred tank was experimentally demonstrated for the manufacture of l-asparagine monohydrate (LAM) crystals with the objective of obtaining a target flattop size distribution. The dual impinging jets combined hot and cold saturated solutions to generate highly uniform 20-μm crystals that were further grown to a desired size in the stirred tank with suppressed nucleation that was instrumented with attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and focused beam reflectance measurement (FBRM). The construction of calibration models and the measurement of solubility and metastable limit were obtained by an automated system that followed preset supersaturation profiles using feedback control. The experiments confirm that greatly enhanced control of the crystal size distribution can be achieved using continuous seeding.

AB - A semi-continuous crystallizer configuration that combines continuous seeding using a dual impinging jet with growth rate control in a stirred tank was experimentally demonstrated for the manufacture of l-asparagine monohydrate (LAM) crystals with the objective of obtaining a target flattop size distribution. The dual impinging jets combined hot and cold saturated solutions to generate highly uniform 20-μm crystals that were further grown to a desired size in the stirred tank with suppressed nucleation that was instrumented with attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and focused beam reflectance measurement (FBRM). The construction of calibration models and the measurement of solubility and metastable limit were obtained by an automated system that followed preset supersaturation profiles using feedback control. The experiments confirm that greatly enhanced control of the crystal size distribution can be achieved using continuous seeding.

KW - Concentration feedback control

KW - Crystallization

KW - Crystallizer design

KW - Dual impinging jets

KW - Pharmaceuticals

KW - Process intensification

UR - https://www.scopus.com/pages/publications/84862901159

U2 - 10.1016/j.ces.2011.12.033

DO - 10.1016/j.ces.2011.12.033

M3 - Article

AN - SCOPUS:84862901159

SN - 0009-2509

VL - 77

SP - 2

EP - 9

JO - Chemical Engineering Science

JF - Chemical Engineering Science

ER -

Towards achieving a flattop crystal size distribution by continuous seeding and controlled growth

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Keywords

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