Importance of macromixing in batch cooling crystallization

Bohlin, Markus; Rasmuson, Åke C.

doi:10.1002/aic.690420310

Cited by 13 publications

(14 citation statements)

References 21 publications

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“…The influence of the mass of seeds on particle size was investigated in two simulation papers. Bohlin and Rasmuson [10] concluded that as the mass of seeds increases, the mean size of the final products may increase or decrease; this finding is similar to the results of the present work. In a word, the effect of the mass of seeds may be explained due to the domination of secondary nucleation mechanisms [11].…”

Section: Effect Of Mass Of Seedssupporting

confidence: 91%

Optimizing the Aspect Ratio of Cephalexin in Reactive Crystallization by Controlling Supersaturation and Seeding Policy

Shang

Hou

2019

Trans. Tianjin Univ.

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Batch crystallization in acidic aqueous solution of cephalexin was conducted by reactive crystallization with or without seeding. Supersaturation was generated by mixing ammonia and acidic aqueous solution of cephalexin and controlled by solution feeding rate and seeding conditions. UV and Morphologi G3 were used to measure supersaturation and aspect ratio. Experimental results demonstrated that burst nucleation occurred and the products were needle-like at high supersaturation; meanwhile, the products were plate-like and had high aspect ratio at low supersaturation. Analysis of the measured supersaturation profiles and corresponding aspect ratio explained the mechanisms governing the aspect ratio. The optimized operating parameters were also proposed (seeding supersaturation is equal to 1.3, seed mass ratio 8% and feeding rate 368 μL/min).

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Section: Effect Of Mass Of Seedssupporting

confidence: 91%

Optimizing the Aspect Ratio of Cephalexin in Reactive Crystallization by Controlling Supersaturation and Seeding Policy

Shang

Hou

2019

Trans. Tianjin Univ.

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“…Given that T was associated with a particular saturated concentration, C *, based on the C vs T solubility curve in Figure a, C * could also be viewed as a decreasing function of time t . The maximum allowable acetaminophen concentration, C , in a well-mixed system as case II, was lower than the one in a nonagitated system as case I at any time t , due to negligible spatial variations in local supersaturation . This was clearly supported by the clearance between the concentration, C , and the calculated saturated concentration, C* , profiles (red and purple dashed curves, Figures and ), representing for the maximum supersaturation, Δ C max = C – C * (i.e., the metastable zone width) at any time, t .…”

Section: Resultsmentioning

confidence: 75%

“…Given that T was associated with a particular saturated concentration, C*, based on the C vs T solubility curve in Figure 2a, C* could also be viewed as a decreasing function of time t. The maximum allowable acetaminophen concentration, C, in a well-mixed system as case II, was lower than the one in a nonagitated system as case I at any time t, due to negligible spatial variations in local supersaturation. 48 This was clearly supported by the clearance between the concentration, C, and the calculated saturated concentration, C*, profiles (red and purple dashed curves, Figures 3 and 4), representing for the maximum supersaturation, ΔC max = C − C* (i.e., the metastable zone width) 49 at any time, t. Unlike the conditions in case II, where the two profiles were overlapped in the early crystallization (red and purple dashed curves in region b, Figure 4), the two profiles in case I were far apart (red and purple dashed curves in region b, Figure 3), indicating that the metastable zone width was much broader in case I at any time, t. Hence, the local ΔC max in case I could get very large and lead to high primary nucleation rates, B°, with many nuclei but insufficient growth, according to the power law relationship: 49…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Engineering Reaction and Crystallization and the Impact on Filtration, Drying, and Dissolution Behaviors: The Study of Acetaminophen (Paracetamol) by In-Process Controls

Lee

Lin

Lee

2013

Org. Process Res. Dev.

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Acetaminophen was synthesized by reacting p-aminophenol with acetic anhydride. Overall materials balance was compiled. Three different crystallization paths (i.e., cases I, II, and III) involving various modes in agitation and addition of sodium hydroxide were taken to produce acetaminophen particles with different particle size distributions (PSDs) and polymorphism. The concentration profile of acetaminophen, temperature, and pH values throughout reaction and crystallization were monitored mainly by in-process control (IPC). The rates of nucleation, crystal growth, and agglomeration during crystallization were quantified by the mixed-suspension mixed-product removal (MSMPR) formalism. The average specific cake resistance for filtration, Krischer rate-moisture plot for drying, Carr's index for powder flowability, and dissolution rate for drug delivery of acetaminophen crystals generated in cases I, II, and III were thoroughly studied and compared. ■ INTRODUCTIONIsolation and purification of solid intermediates and final product from chemical reaction are often achieved by crystallization followed immediately afterwards. 1−3 Reaction crystallization can be thought of as a bottom-up fabrication 4,5 spanning over an enormous time and length scale 6 from the production of angstrom leveled molecules to the generation of nanometer sized nuclei and the growth of submicrometer-sized primary crystals, and all the way up to the generation of micrometer-sized agglomerates. Besides the reaction-related factors such as the completion of reaction, the impurity profiles and levels, and the optimization of yield, 7 other significant engineering impacts brought about by the solid state properties of the final crystallization product, such as polymorphism, 8 crystal habit, particle size, and distribution, 9 on the downstream behaviors 10 involving filter cake resistance, 9,11 drying kinetics, 12 flowability, 13,14 and dissolution rate 5 should be fully considered for ensuring rugged and reproducible scale-up operations. Many of the previous efforts have already been placed on those separate areas, for example: (a) chemical preparation, 15,16 (b) impurity effect on crystallization kinetics, 17 (c) crystallization route on polymorphism, 18,19 (d) solvent selection on crystal habits and agglomerates, 20−22 (e) agitation speed and antisolvent feeding rate on agglomeration, 23 (f) different types of crystallizers on crystal size distribution (CSD), 24 (g) optimization of particle size distribution (PSD), 25 (h) prediction on agglomerate type, 26 (i) rates of nucleation, growth, and aggregation, 27,28 (j) spherical agglomeration, 29 (k) drying of drug substances, 30,31 and (l) crystal growth kinetics and dissolution behavior. 32,33 However, making stable and reproducible pharmaceutical products required monitoring and controlling of the desired PSD from crystallization all the way through various agitated dryers. 34,35 The collective behaviors manifested by different PSDs in blending, wet granulation, and dissolution have also been inve...

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“…The optimal agitation is the minimum stirring rate needed to keep all crystal particles suspended from the bottom. Therefore, the size distribution and concentration of particles vary within an agitated suspension according to the dynamical state of the medium [ 46 ]. Stirring rate can affect seriously the tomographic signals by creating disturbances in the medium.…”

Section: Reactive Crystallisation Imagingmentioning

confidence: 99%

“…Stirring rate can affect seriously the tomographic signals by creating disturbances in the medium. Usually swirls are created which affects the signals and subsequently the reconstructions [ 22 , 43 , 46 ]. Assessing the stirring rate of the 20 cm tank, a few different rates of stirring were applied while recording.…”

Section: Reactive Crystallisation Imagingmentioning

confidence: 99%

Ultrasonic Time-of-Flight Computed Tomography for Investigation of Batch Crystallisation Processes

Koulountzios

Rymarczyk²,

Soleimani

2021

Sensors

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Crystallisation is a crucial step in many industrial processes. Many sensors are being investigated for monitoring such processes to enhance the efficiency of them. Ultrasound techniques have been used for particle sizing characterization of liquid suspensions, in crystallisation process. An ultrasound tomography system with an array of ultrasound sensors can provide spatial information inside the process when compared to single-measurement systems. In this study, the batch crystallisation experiments have been conducted in a lab-scale reactor in calcium carbonate crystallisation. Real-time ultrasound tomographic imaging is done via a contactless ultrasound tomography sensor array. The effect of the injection rate and the stirring speed was considered as two control parameters in these crystallisation functions. Transmission mode ultrasound tomography comprises 32 piezoelectric transducers with central frequency of 40 kHz has been used. The process-based experimental investigation shows the capability of the proposed ultrasound tomography system for crystallisation process monitoring. Information on process dynamics, as well as process malfunction, can be obtained via the ultrasound tomography system.

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Importance of macromixing in batch cooling crystallization

Cited by 13 publications

References 21 publications

Optimizing the Aspect Ratio of Cephalexin in Reactive Crystallization by Controlling Supersaturation and Seeding Policy

Optimizing the Aspect Ratio of Cephalexin in Reactive Crystallization by Controlling Supersaturation and Seeding Policy

Engineering Reaction and Crystallization and the Impact on Filtration, Drying, and Dissolution Behaviors: The Study of Acetaminophen (Paracetamol) by In-Process Controls

Ultrasonic Time-of-Flight Computed Tomography for Investigation of Batch Crystallisation Processes

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