Crystallization diagram for antisolvent crystallization of lactose: using design of experiments to investigate continuous mixing- induced supersaturation

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Abstract

This study investigates the effects of key process parameters of continuous mixing-induced supersaturation on the antisolvent crystallization of lactose using D-optimal Design of Experiments (DoE). Aqueous solutions of lactose were mixed isothermally with antisolvents using a concentric capillary mixer. Process parameters investigated were the choice of antisolvent (acetone or isopropanol), concentration of lactose solution, total mass flow rate, and the ratio of mass flow rates of lactose solution and antisolvent. Using a D-optimal DoE a statistically significant sample set was chosen to explore and quantify the effects of these parameters. The responses measured were the solid state of the lactose crystallized, induction time, solid yield and particle size. Mixtures of α-lactose monohydrate and β-lactose were crystallized under most conditions with β-lactose content increasing with increasing amount of antisolvent. Pure α-lactose monohydrate was crystallized using acetone as the antisolvent, with mass flow ratios near 1:1, and near saturated solutions of lactose. A higher resolution DoE was adopted for acetone and was processed using multivariate methods to obtain a crystallization diagram of lactose. The model was used to create an optimized process to produce α-lactose monohydrate and predicted results agreed well with those obtained experimentally, validating the model. The solid state of lactose, induction time, and solid yield were accurately predicted.
LanguageEnglish
Pages2611-2621
Number of pages11
JournalCrystal Growth and Design
Volume17
Issue number5
Early online date28 Mar 2017
DOIs
Publication statusPublished - 3 May 2017

Fingerprint

lactose
experiment design
Supersaturation
Lactose
Crystallization
supersaturation
Design of experiments
diagrams
Acetone
crystallization
Flow rate
acetone
Particle size
mass flow rate
induction
solid state
2-Propanol
mass flow
Optimal design

Keywords

  • continuous mixing-induced supersaturation
  • antisolvent crystallization
  • lactose
  • concentric capillary mixer
  • D-optimal design of experiments
  • induction time
  • solid yield

Cite this

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title = "Crystallization diagram for antisolvent crystallization of lactose: using design of experiments to investigate continuous mixing- induced supersaturation",
abstract = "This study investigates the effects of key process parameters of continuous mixing-induced supersaturation on the antisolvent crystallization of lactose using D-optimal Design of Experiments (DoE). Aqueous solutions of lactose were mixed isothermally with antisolvents using a concentric capillary mixer. Process parameters investigated were the choice of antisolvent (acetone or isopropanol), concentration of lactose solution, total mass flow rate, and the ratio of mass flow rates of lactose solution and antisolvent. Using a D-optimal DoE a statistically significant sample set was chosen to explore and quantify the effects of these parameters. The responses measured were the solid state of the lactose crystallized, induction time, solid yield and particle size. Mixtures of α-lactose monohydrate and β-lactose were crystallized under most conditions with β-lactose content increasing with increasing amount of antisolvent. Pure α-lactose monohydrate was crystallized using acetone as the antisolvent, with mass flow ratios near 1:1, and near saturated solutions of lactose. A higher resolution DoE was adopted for acetone and was processed using multivariate methods to obtain a crystallization diagram of lactose. The model was used to create an optimized process to produce α-lactose monohydrate and predicted results agreed well with those obtained experimentally, validating the model. The solid state of lactose, induction time, and solid yield were accurately predicted.",
keywords = "continuous mixing-induced supersaturation, antisolvent crystallization, lactose, concentric capillary mixer, D-optimal design of experiments, induction time, solid yield",
author = "P{\'o}l Macfhionnghaile and Vaclav Svoboda and John McGinty and Alison Nordon and Jan Sefcik",
year = "2017",
month = "5",
day = "3",
doi = "10.1021/acs.cgd.7b00136",
language = "English",
volume = "17",
pages = "2611--2621",
journal = "Crystal Growth and Design",
issn = "1528-7483",
publisher = "American Chemical Society",
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T2 - Crystal Growth and Design

AU - Macfhionnghaile, Pól

AU - Svoboda, Vaclav

AU - McGinty, John

AU - Nordon, Alison

AU - Sefcik, Jan

PY - 2017/5/3

Y1 - 2017/5/3

N2 - This study investigates the effects of key process parameters of continuous mixing-induced supersaturation on the antisolvent crystallization of lactose using D-optimal Design of Experiments (DoE). Aqueous solutions of lactose were mixed isothermally with antisolvents using a concentric capillary mixer. Process parameters investigated were the choice of antisolvent (acetone or isopropanol), concentration of lactose solution, total mass flow rate, and the ratio of mass flow rates of lactose solution and antisolvent. Using a D-optimal DoE a statistically significant sample set was chosen to explore and quantify the effects of these parameters. The responses measured were the solid state of the lactose crystallized, induction time, solid yield and particle size. Mixtures of α-lactose monohydrate and β-lactose were crystallized under most conditions with β-lactose content increasing with increasing amount of antisolvent. Pure α-lactose monohydrate was crystallized using acetone as the antisolvent, with mass flow ratios near 1:1, and near saturated solutions of lactose. A higher resolution DoE was adopted for acetone and was processed using multivariate methods to obtain a crystallization diagram of lactose. The model was used to create an optimized process to produce α-lactose monohydrate and predicted results agreed well with those obtained experimentally, validating the model. The solid state of lactose, induction time, and solid yield were accurately predicted.

AB - This study investigates the effects of key process parameters of continuous mixing-induced supersaturation on the antisolvent crystallization of lactose using D-optimal Design of Experiments (DoE). Aqueous solutions of lactose were mixed isothermally with antisolvents using a concentric capillary mixer. Process parameters investigated were the choice of antisolvent (acetone or isopropanol), concentration of lactose solution, total mass flow rate, and the ratio of mass flow rates of lactose solution and antisolvent. Using a D-optimal DoE a statistically significant sample set was chosen to explore and quantify the effects of these parameters. The responses measured were the solid state of the lactose crystallized, induction time, solid yield and particle size. Mixtures of α-lactose monohydrate and β-lactose were crystallized under most conditions with β-lactose content increasing with increasing amount of antisolvent. Pure α-lactose monohydrate was crystallized using acetone as the antisolvent, with mass flow ratios near 1:1, and near saturated solutions of lactose. A higher resolution DoE was adopted for acetone and was processed using multivariate methods to obtain a crystallization diagram of lactose. The model was used to create an optimized process to produce α-lactose monohydrate and predicted results agreed well with those obtained experimentally, validating the model. The solid state of lactose, induction time, and solid yield were accurately predicted.

KW - continuous mixing-induced supersaturation

KW - antisolvent crystallization

KW - lactose

KW - concentric capillary mixer

KW - D-optimal design of experiments

KW - induction time

KW - solid yield

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