Strategy for Fast Decision on Material System Suitability for Continuous Crystallization Inside a Slug Flow Crystallizer
<p><math display="inline"><semantics> <mi>Θ</mi> </semantics></math><sub>stat</sub> for the respective solvents is shown. The grey marked area indicates the region in which <math display="inline"><semantics> <mi>Θ</mi> </semantics></math><sub>stat</sub> measurements were not possible (<math display="inline"><semantics> <mi>Θ</mi> </semantics></math><sub>stat</sub> < 20°) with the method described before in <a href="#sec4dot1-micromachines-13-01795" class="html-sec">Section 4.1</a>. The green area (<math display="inline"><semantics> <mi>Θ</mi> </semantics></math><sub>stat</sub> ≥ 90°) marks the <math display="inline"><semantics> <mi>Θ</mi> </semantics></math><sub>stat</sub> at which a non-wetting behavior is expected, and a stable slug flow might be generated.</p> "> Figure 2
<p>Schematic setup for the validation of solvent suitability for slug flow crystallization.</p> "> Figure 3
<p>Images of slugs at the end of the apparatus (<span class="html-italic">L</span> = 7.5 m) during operation with different solvents in an FEP tubing. The liquid and gas flow rates were set to <span class="html-italic">Q</span> = 10 mL min<sup>−1</sup> each. The experiments were conducted at ambient temperature (<math display="inline"><semantics> <mi>ϑ</mi> </semantics></math><sub>amb</sub> <math display="inline"><semantics> <mo>≈</mo> </semantics></math> 22 °C).</p> "> Figure 4
<p>Calculated <span class="html-italic">Ca</span> numbers for the tested solvents in the SFC. The calculation was performed for the operating parameters based on the slug flow stability experiments at liquid and gas flow rates of <span class="html-italic">Q</span> = 10 mL min<sup>−1</sup> each and a ambient temperature of <math display="inline"><semantics> <mi>ϑ</mi> </semantics></math><sub>amb</sub> <math display="inline"><semantics> <mo>≈</mo> </semantics></math> 22 °C. The green area marks the dry pattern slug flow range according to the limit of <span class="html-italic">Ca</span> < 10<sup>−3</sup>.</p> "> Figure 5
<p>Images of saturated Arg/water (<b>top</b>) and APAP/water (<b>bottom</b>) slugs at the end of the apparatus (<span class="html-italic">L</span><sub>tubing</sub> = 7.5 m) during operation inside an FEP tubing of SFC. The liquid and gas flow rates were set to <span class="html-italic">Q</span> = 10 mL min<sup>−1</sup> each. The experiments were conducted at ambient temperature (<math display="inline"><semantics> <mi>ϑ</mi> </semantics></math><sub>amb</sub> <math display="inline"><semantics> <mo>≈</mo> </semantics></math> 22 °C).</p> "> Figure 6
<p>Solubilities of Ala (gray), Arg (blue), and APAP (green) in water (<b>a</b>) and ethanol (<b>b</b>) at 0.1 MPa: Down-pointing triangles, diamonds, circles, up-pointing triangles, and stars depict measured solubilities in water from An et al. [<a href="#B61-micromachines-13-01795" class="html-bibr">61</a>], Grosse Daldrup et al. [<a href="#B74-micromachines-13-01795" class="html-bibr">74</a>], Amend and Helgeseon [<a href="#B75-micromachines-13-01795" class="html-bibr">75</a>], Granberg et al. [<a href="#B76-micromachines-13-01795" class="html-bibr">76</a>], and Grant et al. [<a href="#B42-micromachines-13-01795" class="html-bibr">42</a>]. Hexagons, squares, and left-pointing triangles denote solubility measurements in ethanol from An et al. [<a href="#B61-micromachines-13-01795" class="html-bibr">61</a>], Granberg et al. [<a href="#B53-micromachines-13-01795" class="html-bibr">53</a>], and Matsuda et al. [<a href="#B77-micromachines-13-01795" class="html-bibr">77</a>]. Pentagons and right-pointing triangles are measurements in water and in ethanol performed in this work, respectively. The solid lines are modeled solubility lines using PC-SAFT.</p> "> Figure 7
<p>Ternary phase diagram of Ala/water/ethanol at 0.1 MPa with compositions given in mass fractions: Solubility lines were predicted in this work using PC-SAFT, and symbols denote solubility measurements from An et al. [<a href="#B61-micromachines-13-01795" class="html-bibr">61</a>]. The arrow indicates the direction of increasing temperature from 10 °C to 20 °C, 30 °C, 40 °C, and 50 °C.</p> "> Figure 8
<p>The <span class="html-italic">Ca</span> number is plotted against the <math display="inline"><semantics> <mi>Θ</mi> </semantics></math><sub>stat</sub> for different EtOH/water compositions and volume flow rates. Delineations for the dry pattern are shown via the black dashed lines based on the literature (<b>a</b>) and based on the observations in this work (<b>b</b>). The green area marks the dry pattern, the white area the transition, and the gray area the wet region. The latter is unsuitable for crystallization in the SFC.</p> "> Figure 9
<p>Depiction of the slug flow obtained in the experiments for evaluating the slug shape for different compositions of ethanol/water mixtures at a total volumetric flow rate of <span class="html-italic">Q</span><sub>tot</sub> = 20 mL min<sup>−1</sup> at ambient temperature (<math display="inline"><semantics> <mi>ϑ</mi> </semantics></math><sub>amb</sub> <math display="inline"><semantics> <mo>≈</mo> </semantics></math> 22 °C).</p> ">
Abstract
:1. Introduction
- (1)
- Pre-selection of solvents for the crystallization of the desired solid compound
- (2)
- Static contact angle measurements
- (3)
- Proof of slug flow stability inside the apparatus
- (4)
- Solubility modeling
2. Substances Used
3. Modeling of Solubilities Using PC-SAFT Equation of State
4. Strategy for Solvent Selection
4.1. Static Contact Angle Measurements
Results of Static Contact Angle Measurements
4.2. Proof of Stable Slug Flow Inside SFC
Results of Proof of Slug Flow Stability
4.3. Proving the Operability of Slug Flow Crystallizer with the Solutes
4.4. Solubilities for Binary Systems
5. Consideration of Ternary Systems for Slug Flow Crystallizer Application
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
A | Association site |
assoc | Association |
Ac | Acetone |
Ala | l-alanine |
amb | Ambient |
APAP | Acetaminophen |
API | Active pharmaceutical ingredient |
Arg | l-arginine |
B | Association site |
b | Intercept |
disp | Dispersion |
dyn | Dynamic contact angle |
EtOH | Ethanol |
FEP | Fluorinated ethylene propylene |
hc | Hard chain |
i | Component i |
IPA | Isopropanol |
j | Component j |
L | Liquid phase |
m | Slope |
MSMPR | Mixed-suspension mixed-product removal |
PC-SAFT | Perturbed-chain statistical associating fluid theory |
PFC | Plug-flow crystallizer |
PP | Polypropylene |
PSD | Particle size distribution |
PVC | Polyvinyl chloride |
res | Residual |
RTD | Residence time distribution |
RTDL | Residence time distribution of the liquid phase |
RTDS | Residence time distribution of the solid phase |
S | Solid phase |
SFC | Slug flow crystallizer |
stat | Static contact angle |
wat | Water |
Latin Symbols
a | Helmholtz energy/J mol−1 |
Concentration/g g−1 | |
Saturation concentration/g g−1 | |
Ca | Capillary number/- |
cp | Heat capacity/J mol−1 |
dh | Hydraulic diameter/mm |
di | Inner diameter/mm |
dout | Outer diameter/mm |
Eö | Eötvös number/- |
h | Enthalpy/J mol−1 |
k | Interaction parameter/- |
kB | Boltzmann constant/J K−1 |
L50 | Median slug length |
L90-10 | Width of slug length |
Ltubing | Length of tubing/m |
M | Molar mass/g mol−1 |
mseg | Segment number/- |
N | Number of sites/- |
Qair | Gas volume flow rate/mL min−1 |
Qliq | Liquid volume flow rate/mL min−1 |
Qtot | Total volume flow rate/mL min−1 |
R | Universal gas constant/J mol−1 K−1 |
T | Temperature/K |
u | Flow velocity/m s−1 |
u | Dispersion energy/J mol−1 |
w | Mass fraction/wt.-% |
x | Mole fraction/mol mol−1 |
Greek Symbols
η | Dynamic viscosity/Pa s |
Θ | Three-phase contact angle/° |
Slope of linear temperature-dependent heat capacity/J mol−1 K−2 | |
Intercept of linear temperature-dependent heat capacity/J mol−1 K−1 | |
Gas–liquid interfacial tension/N m−1 | |
Solid–gas interfacial tension/N m−1 | |
Solid–liquid interfacial tension/N m−1 | |
Temperature/°C | |
Saturation temperature/°C | |
Activity coefficient/- | |
Association energy/J mol−1 | |
Association volume/- | |
Segment diameter/Å |
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Component | ||||
---|---|---|---|---|
Ala | 608.0 [52] | 25.99 [50] | −0.057 [50] | 39.923 [50] |
Arg | 558.0 [50] | 32.00 [50] | −0.364 [50] | 237.991 [50] |
APAP | 443.6 [53] | 27.10 [53] | 0 1 | 99.800 [54] |
Component | |||||||
---|---|---|---|---|---|---|---|
Ala [56] | 89.090 | 0.0613 | 2.5222 | 287.590 | 3176.600 | 0.0819 | 1/1 |
Arg [56] | 174.210 | 0.0569 | 2.6572 | 349.710 | 2555.450 | 0.0393 | 3/1 |
APAP [57] | 151.160 | 0.0498 | 3.5080 | 398.284 | 1994.200 | 0.0100 | 2/2 |
Water [58] | 18.015 | 0.0669 | * | 353.950 | 2425.700 | 0.0451 | 1/1 |
Ethanol [55] | 46.069 | 0.0517 | 3.1770 | 198.237 | 2653.384 | 0.0320 | 1/1 |
Mixture | ||
---|---|---|
Ala/water [56] | 2.910 × 10−4 | −0.147962 |
Ala/ethanol 1 | 1.140 × 10−3 | −0.3513 |
Arg/water [56] | 0 | −0.0145 |
Arg/ethanol 2 | 2.075 × 10−4 | −0.134529 |
APAP/water [63] | 1.770 × 10−4 | −0.051 |
APAP/ethanol 3 | 1.250 × 10−4 | −0.08764 |
water/ethanol [64] | 6.860 × 10−4 | −0.2662 |
stat/° Glass | stat/° Aluminum | stat/° Polystyrene | stat/° Silicone | stat/° FEP | |
---|---|---|---|---|---|
n-Hexane | <20 | <20 | <20 | <20 | <20 |
Isopropanol | <20 | <20 | <20 | <20 | 36.65 ± 1.37 |
Acetone | <20 | <20 | <20 | <20 | 47.33 ± 3.48 |
Ethanol | <20 | <20 | <20 | 23.10 ± 1.34 | 45.51 ± 3.68 |
Water | 20.89 ± 1.09 | 66.44 ± 1.41 | 81.98 ± 0.43 | 97.99 ± 0.38 | 100.66 ± 1.37 |
L50/mm | L90-10/mm | |
---|---|---|
n-Hexane | 10.70 | 2.23 |
Isopropanol | 24.30 | 1.27 |
Acetone | 16.37 | 2.45 |
Ethanol | 20.58 | 0.85 |
Water | 10.16 | 0.99 |
Solvent | dyn/° Receding | dyn/° Advanced | CAHmax/° |
---|---|---|---|
n-Hexane | 20–34 | 25–36 | 16 |
Isopropanol | 36–63 | 47–64 | 28 |
Acetone | 50–60 | 65–73 | 23 |
Ethanol | 26–41 | 40–56 | 30 |
Water | 82–92 | 84–92 | 10 |
wEtOH/ wt.-% | stat/° FEP | Volume Flow Rate/ mL min−1 | / - | Flow Pattern Based on Literature Limit (Ca < 10−3) | Flow Pattern Based on Experiments | Slug Form Mechanism | CAHmax/ - |
---|---|---|---|---|---|---|---|
0 | 100.66 ± 1.37 | 20 | 5.83∙10−4 | Dry | Dry | Squeezing | 10 |
30 | 8.74∙10−4 | Dry | Dry | Squeezing | 9 | ||
40 | 1.17∙10−3 | Wet | Dry | Squeezing | 9 | ||
60 | 1.75∙10−3 | Wet | Dry | Squeezing | 10 | ||
10 | 89.64 ± 4.10 | 20 | 1.18∙10−3 | Wet | Dry | Squeezing | 7 |
30 | 1.77∙10−3 | Wet | Dry | Squeezing | 11 | ||
40 | 2.36∙10−3 | Wet | Dry | Squeezing | 8 | ||
60 | 3.55∙10−3 | Wet | Dry | Transition | 11 | ||
20 | 83.39 ± 1.96 | 20 | 2.09∙10−3 | Wet | Dry | Transition | 12 |
30 | 3.14∙10−3 | Wet | Dry | Transition | 12 | ||
40 | 4.19∙10−3 | Wet | Dry | Transition | 9 | ||
60 | 6.28∙10−3 | Wet | Dry | Dripping | 16 | ||
30 | 78.65 ± 1.84 | 20 | 3.07∙10−3 | Wet | Dry | Transition | 13 |
30 | 4.61∙10−3 | Wet | Dry | Transition | 10 | ||
40 | 6.15∙10−3 | Wet | Dry | Dripping | 12 | ||
60 | 9.22∙10−3 | Wet | Wet | Dripping | 19 | ||
50 | 44.20 ± 2.74 | 20 | 4.25∙10−3 | Wet | Dry | Dripping | 13 |
30 | 6.37∙10−3 | Wet | Wet | Dripping | 21 | ||
40 | 8.49∙10−3 | Wet | Wet | Dripping | 19 | ||
60 | 1.27∙10−2 | Wet | Wet | Dripping | 17 |
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Kufner, A.C.; Krummnow, A.; Danzer, A.; Wohlgemuth, K. Strategy for Fast Decision on Material System Suitability for Continuous Crystallization Inside a Slug Flow Crystallizer. Micromachines 2022, 13, 1795. https://doi.org/10.3390/mi13101795
Kufner AC, Krummnow A, Danzer A, Wohlgemuth K. Strategy for Fast Decision on Material System Suitability for Continuous Crystallization Inside a Slug Flow Crystallizer. Micromachines. 2022; 13(10):1795. https://doi.org/10.3390/mi13101795
Chicago/Turabian StyleKufner, Anne Cathrine, Adrian Krummnow, Andreas Danzer, and Kerstin Wohlgemuth. 2022. "Strategy for Fast Decision on Material System Suitability for Continuous Crystallization Inside a Slug Flow Crystallizer" Micromachines 13, no. 10: 1795. https://doi.org/10.3390/mi13101795