Growth Rate Measurements of Organic Crystals in a Cone‐Shaped Fluidized‐Bed Cell

Ostermann, M.; Termühlen, Maren; Schembecker, Gerhard; Wohlgemuth, Kerstin

doi:10.1002/ceat.201700683

Cited by 12 publications

(9 citation statements)

References 38 publications

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“…According to the procedure presented by Ostermann et al, l -alanine seed crystals were prepared . A mixture of ethanol and ultrapure water with a volume ratio of 4/1 and ethanol absolute (Merck KGaA, absolute EMPLURA) both at 25 °C were utilized as wash liquids as described by Terdenge and Wohlgemuth. , For subsequent drying, the washed crystals were transferred to a crystallizing dish and predried in a drying oven at 50 °C.…”

Section: Methodsmentioning

confidence: 99%

Characterization of a Modular Continuous Vacuum Screw Filter for Small-Scale Solid–Liquid Separation of Suspensions

Steenweg

Seifert

Schembecker

et al. 2021

Org. Process Res. Dev.

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A key enabler for the future success of continuous manufacturing in pharmaceutical and fine chemical production processes is the control of product quality. Since approx. 90% of all small molecular active pharmaceutical ingredients produced involve a crystallization step, a holistic view on its process chain is crucial in order to ensure a defined particle size distribution, high purity, and specific polymorphic form. Different concepts for small-scale continuous crystallization are available, improving the product qualities in comparison to batch. Continuous solid–liquid separations, on the other hand, are rather scarce. Therefore, we designed and characterized an innovative continuous vacuum screw filter (CVSF) for solid–liquid separation, washing, and drying of suspensions in a small scale (up to 10 g of solid per minute). This contribution shows the general working principle of the CVSF as well as a systematic investigation of varying operating parameters on the particle size distribution (PSD), residual moisture, and residence time distribution of the solid phase. As a model system, l-alanine/water is used. The results show that the PSD can be entirely maintained while ensuring a narrow residence time distribution of the solid phase with axial dispersion numbers between 18.7 and 76.2. The residual moisture is for all experiments in a good range of 20–25%. Furthermore, it could be shown that the operability is possible over 8 h. Summarizing, the modular setup of the CVSF offers a maximized flexibility and thus rapid adaptability to changing market demands and product requirements.

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Section: Methodsmentioning

confidence: 99%

Characterization of a Modular Continuous Vacuum Screw Filter for Small-Scale Solid–Liquid Separation of Suspensions

Steenweg

Seifert

Schembecker

et al. 2021

Org. Process Res. Dev.

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“…For the CVSF characterization experiments, recrystallized and sieved (355–560 μm, ε = 0.451) L -alanine (Evonik Industries AG, 99.7% purity, ρ S = 1420 kg m –3 ) crystals were resuspended in a saturated L -alanine/water solution (ρ ML = 1042 kg m –3 , η ML = 1.61 mPa s) at a room temperature of approximately 21 °C. The L -alanine crystals were prepared as presented by Ostermann et al…”

Section: Materials and Methodsmentioning

confidence: 99%

Process Intensification Enabling Continuous Manufacturing Processes Using Modular Continuous Vacuum Screw Filter

Steenweg

Seifert

Böttger

et al. 2021

Org. Process Res. Dev.

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A novel apparatus concept for integrated, small-scale continuous filtration, washing, and drying is presented. The continuous vacuum screw filter (CVSF) allows obtaining dried and free-flowing product particles from the continuously fed suspension. While the first study presented the CVSF concept in detail and focused on the characterization with respect to the product quality control and solid-phase residence time distribution (RTD S ) during sole filtration, the modular extension with washing modules and a vacuum-induced (pre-) drying setup is now presented here. For this purpose, a wash module was designed and implemented. The influence of single-stage and two-stage washing on the particle size distribution (PSD) and RTD S was investigated for the L-alanine/water model system. Single-stage washing increased the particle size of d 90,3 by 120 μm (+19%) due to a higher agglomeration degree, while using two-stage washing could completely preserve the particulate properties of the inlet suspension. To identify favorable operating conditions for efficient (pre-) drying, the effect of varying throughputs and mean residence times on the residual moisture of the product particles was quantified. High filling degrees (>30%) and increased mean residence times (>11 min), in combination with two-stage washing and efficient vacuum-induced airflow, ensured completely isolated, free-flowing, and almost dry particles with residual moistures of 1% and an entire maintenance of the PSD. Measurements of the RTD S showed a slight broadening due to the wash liquid used, still ensuring a narrow RTD S and thus almost plug-flow-like behavior. In summary, the CVSF offers unique features, such as its modularity and rapid start-up behavior, providing a promising concept for integrated continuous particle isolation from suspensions.

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“…As solid phase, L-alanine seed crystals are employed that are prepared according to Ostermann's procedure [29]. Here, practicable crystal product sizes attainable in the ATC comprise sieve fractions 100-160 µm and 250-315 µm.…”

Section: Methodsmentioning

confidence: 99%

Flow Map for Hydrodynamics and Suspension Behavior in a Continuous Archimedes Tube Crystallizer

et al. 2021

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The Archimedes Tube Crystallizer (ATC) is a small-scale coiled tubular crystallizer operated with air-segmented flow. As individual liquid segments are moved through the apparatus by rotation, the ATC operates as a pump. Thus, the ATC overcomes pressure drop limitations of other continuous crystallizers, allowing for longer residence times and crystal growth phases. Understanding continuous crystallizer phenomena is the basis for a well-designed crystallization process, especially for small-scale applications in the pharmaceutical and fine chemical industry. Hydrodynamics and suspension behavior, for example, affect agglomeration, breakage, attrition, and ultimately crystallizer blockage. In practice, however, it is time-consuming to investigate these phenomena experimentally for each new material system. In this contribution, a flow map is developed in five steps through a combination of experiments, CFD simulations, and dimensionless numbers. Accordingly, operating parameters can be specified depending on ATC design and material system used, where suspension behavior is suitable for high-quality crystalline products.

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Growth Rate Measurements of Organic Crystals in a Cone‐Shaped Fluidized‐Bed Cell

Cited by 12 publications

References 38 publications

Characterization of a Modular Continuous Vacuum Screw Filter for Small-Scale Solid–Liquid Separation of Suspensions

Characterization of a Modular Continuous Vacuum Screw Filter for Small-Scale Solid–Liquid Separation of Suspensions

Process Intensification Enabling Continuous Manufacturing Processes Using Modular Continuous Vacuum Screw Filter

Flow Map for Hydrodynamics and Suspension Behavior in a Continuous Archimedes Tube Crystallizer

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