Batch crystallization

Wey, J. S.; Karpiński, Piotr

doi:10.1016/b978-075067012-8/50012-4

Cited by 20 publications

(27 citation statements)

References 30 publications

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“…The total number of crystals (N) for statistical analysis is included. Definition of length and width is the same as in the book [34]., and width is perpendicular to the length on the image. For all these crystals, their standard deviation (SD) and the coefficient of variation (COV) of both the length and width are also included here.…”

Section: Crystal Characterizationmentioning

confidence: 99%

“…Batch crystallizers provide many important pieces of information for guiding the design of continuous crystallizers [30][31][32][33][34]. For example, the solubility curve and crystallization properties (e.g., kinetics) for the specific solute/solvent system are usually derived in batch experiments.…”

Section: Introductionmentioning

confidence: 99%

“…Non-optimum cooling (e.g., crash cooling) was shown in batch crystallizers to generate tiny crystals from secondary nucleation, especially for non-seeded situations [35,36]. In addition, batch experience indicates that organic crystals probably cannot hold their morphology under the shear in the crystallizer, if their longer dimension reaches 20% or larger of the shorter dimension of the crystallizer [6,33,34,37].…”

Section: Introductionmentioning

confidence: 99%

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Continuous Generation of Millimeter-Sized Glycine Crystals in Non-Seeded Millifluidic Slug Flow

Mou

Yang

et al. 2019

Crystals

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Millimeter-sized α-glycine crystals were generated from continuous non-seeded cooling crystallization in slug flow. The crystallization process is composed of three steps in sequence: slug formation, crash-cooling nucleation, and growth. Stable uniform slugs of three different aspect ratios (slug length/tubing inner diameter) were formed, by adjusting the flow rates of both the solution and air streams. Besides supersaturation, the slug aspect ratio can also affect primary nucleation outcome. Stable slug flow can accommodate a relative supersaturation (C/C*) of up to 1.5 without secondary nucleation. Large glycine crystals can grow to millimeter size within 10 min, inside millimeter-sized slugs without reducing the slug quality.

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Section: Crystal Characterizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Continuous Generation of Millimeter-Sized Glycine Crystals in Non-Seeded Millifluidic Slug Flow

Mou

Yang

et al. 2019

Crystals

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“…Compared with evaporative crystallization and cooling crystallization, antisolvent crystallization has the advantage of nearly a constant temperature, although the temperature at the feeding points might vary due to the heat of mixing. Because of the poor solubility of the target active pharmaceutical ingredient in the antisolvent, supersaturation could be quickly induced once the antisolvent is added to the system, leading to the formation of the driving force for crystallization. , This is especially practical for thermally sensitive pharmaceuticals because they can crystallize in large yield without large temperature variations. Furthermore, antisolvent crystallization can produce small uniform crystals, which could improve bioavailability and dissolution rates significantly and avoid polymorph transformation, yield loss, and dust problems caused by grinding …”

Section: Introductionmentioning

confidence: 99%

CFD–PBE Model and Simulation of Continuous Antisolvent Crystallization in an Impinging Jet Crystallizer with a Multiorifice at Different Positions

Chen

Wang

et al. 2021

Ind. Eng. Chem. Res.

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In this study, a comprehensive model which combines CFD and the population balance equation (PBE) was utilized to simulate the paracetamol continuous antisolvent crystallization. PBE was discretized using a high-resolution scheme and solved with the Eulerian multiphase model. The results indicated that the CFD–PBE model could successfully simulate the fluid dynamics, mass transfer, and crystal size distribution in the crystallizer. Based on the previously proposed multiorifice impinging jet crystallizer, an impinging jet crystallizer with a multiorifice at different axial positions was designed and studied in detail. The effects of different operating conditions on the mixing and crystallization were analyzed and discussed. The results obtained in this work can be used to help the design and optimization of the impinging jet crystallizer with a multiorifice at different positions.

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“…Among various crystallization methods, especially in the pharmaceutical industry, the antisolvent crystallization technique has the advantage of inducing crystallization of thermally sensitive pharmaceuticals without generating large temperature variations. , In order to generate higher supersaturation, the antisolvent technique can be combined with cooling crystallization. , Since these methods require rapid and sufficient mixing of the antisolvent with the solute dissolved in solvent, the design and optimization of such crystallizers play an important role in achieving an effective crystallization with controlled CSD.…”

Section: Introductionmentioning

confidence: 99%

openCrys: Open-Source Software for the Multiscale Modeling of Combined Antisolvent and Cooling Crystallization in Turbulent Flow

Rosa

Braatz

2018

Ind. Eng. Chem. Res.

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The open-source software, called openCrys, is provided for the multiscale simulation of antisolvent and combined antisolventcooling crystallization. It simulates the macro-and micromixing scales, and the complete energy and population balance equations during crystal nucleation and growth. The model is based on the Reynolds-Averaged-Navier−Stokes equation, coupled with a three-environment presumed probability density function model, and the spatially varying population balance equation semidiscretized using a high resolution finite-volume method. openCrys is implemented in C++ object oriented programming language using the open-source CFD package OpenFOAM. The software is used to compare the performance of dual impinging jet, coaxial, and radial crystallizers. It is shown that improving the micromixing does not necessarily result in a narrower crystal size distribution when temperature effects are taken into account. The complex interplay of crystallizer kinetics and momentum, mass, and heat transfer makes the selection of the best mixer for a particular application to be nonobvious, which motivates the development and application of high-fidelity multiscale simulations for the design of antisolvent crystallizers.

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Batch crystallization

Cited by 20 publications

References 30 publications

Continuous Generation of Millimeter-Sized Glycine Crystals in Non-Seeded Millifluidic Slug Flow

Continuous Generation of Millimeter-Sized Glycine Crystals in Non-Seeded Millifluidic Slug Flow

CFD–PBE Model and Simulation of Continuous Antisolvent Crystallization in an Impinging Jet Crystallizer with a Multiorifice at Different Positions

openCrys: Open-Source Software for the Multiscale Modeling of Combined Antisolvent and Cooling Crystallization in Turbulent Flow

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