Population balance modeling of unstirred cooling crystallization on an integrated belt filter

Sonnenschein, Jana; Hermes, Mario; Höving, Stefan; Kockmann, Norbert; Wohlgemuth, Kerstin

doi:10.1016/j.compchemeng.2022.108024

Cited by 5 publications

(5 citation statements)

References 24 publications

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“…Simulated temperature profile of an unstirred sucrose suspension as a function of distance from the temperature unit. Adapted from 19.…”

Section: Methodsmentioning

confidence: 99%

“…All experiments involved an unstirred sucrose suspension with a height of 20 mm. The temperature profiles occurring within this suspension were modeled by Sonnenschein et al [19] and can be seen in Fig. 3.…”

Section: Model Substance Systemmentioning

confidence: 99%

“…The approach for modeling the cooling crystallization is based on a spatially resolved population balance equation coupled with solute mass and solute heat balances. A detailed description is given in Sonnenschein et al [19].…”

Section: Modelingmentioning

confidence: 99%

“…Further investigations by Ho ¨ving et al [18] found that Peltier elements allow for precise temperature control of the crystal suspension during the crystallization and that the seed particles and temperature management exert a significant influence on the resulting product crystals. Parallel to experimental investigations, a model for the integrated apparatus was set up by Sonnenschein et al [19] to reduce experimental effort when switching substance systems.…”

Section: Introductionmentioning

confidence: 99%

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From Lab to Pilot Scale: Commissioning of an Integrated Device for the Generation of Crystals

et al. 2023

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Fast time-to-market, increased efficiency, and flexibility of production processes are major motivators for the development of integrated, continuous apparatuses with short changeover times. Following this trend, the modular belt crystallizer was developed and characterized in lab scale with the model system sucrose-water. Based on the promising results, the plant concept was upscaled and commissioned in industrial environment. The results are presented within the scope of this work. Starting from small seed crystals in solution, it was possible to grow, separate, and dry product particles. Further, the conducted experiments demonstrated that it is feasible to transfer the results from laboratory to pilot scale, which in turn enables accelerated process design as well as development.

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“…Simulated temperature profile of an unstirred sucrose suspension as a function of distance from the temperature unit. Adapted from 19.…”

Section: Methodsmentioning

confidence: 99%

Section: Model Substance Systemmentioning

confidence: 99%

Section: Modelingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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From Lab to Pilot Scale: Commissioning of an Integrated Device for the Generation of Crystals

et al. 2023

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“…However, from an applied perspective, several obstacles exist such as strict regulatory procedures, unavailable analytical tools/data, and the lack of time to build a modeling culture. Despite the difficulties, the advantages of PBMs have already been demonstrated in industrial environments, besides others, via modeling semi-industrial and industrial crystallization, − and scaling up of particle processes. , …”

Section: Introductionmentioning

confidence: 99%

Dynamic Modeling and Optimal Design Space Determination of Pharmaceutical Crystallization Processes: Realizing the Synergy between Off-the-Shelf Laboratory and Industrial Scale Data

Orosz,

Szilágyi,

Spaits

et al. 2024

Ind. Eng. Chem. Res.

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Well-designed and operated pharmaceutical crystallization can enhance the key features of the active pharmaceutical ingredients, which can be taken to the next level by a model-based design. Model development not only requires computer implementation, kinetic identification, and advanced programming skills but also a suitable number of information-rich experiments. Numerous products have been crystallized for a long time, with many related laboratory-scale experiments and plant-scale manufacturing data accumulated from past developments and productions. The question arises: can these historical data be utilized to build process models, which can be used subsequently to optimize processes? We aim to demonstrate in this study that this approach can be feasible. To illustrate this, we used the data of two commercial crystallization production campaigns, totaling 16 industrial crystallizations, and six laboratory experiments, four of which were formerly performed for different purposes. Our tailored PBM involves primary and secondary nucleation, crystal growth, and dissolution and can simultaneously reproduce laboratory-and plant-scale dynamics. Despite relying on nontargeted experiments and measuring/sampling strategy, the estimated parameters were accurate, with an average deviation between the nominal values and 95% confidence interval bonds of 16.1%. The model was employed to construct an optimal design space (DS) for a temperature cycling operation involving, as a constraint, 2, 3, and 4 cycles: the goal was to define a temperature domain with minimal batch time and heating/cooling energy demand that respects the constraints on the product PSD and heating/cooling rates. The problem was solved as a constrained robust optimization, where discrete temperature stamps and corresponding time stamps were optimized. The optimal operation halved the current batch time. The optimized temperature profile was validated on a laboratory scale for two particle size specifications. More expansive DS (1 vs 0.5 h random temperature variation allowed around the nominal temperature profile) was observed to translate to longer batch times (30 vs 25 h) and deeper temperature cycles of 40 vs 20 °C, reflecting a tradeoff between nominal performance and robustness. The optimal laboratory-scale operation was validated successfully by repeated experiments.

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Simplified Approach to Characterize the Cooling Crystallization in a Modular Mini-Plant

et al. 2023

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The characterization of new process equipment often includes tedious experiments, particularly for (cooling) crystallization. This can be cost-intensive and time-consuming when the actual equipment has to be continuously operated to gain new insights. For multi-purpose plants that frequently change the process substance system, this can be especially laborious. In order to accelerate the generation of characterization data for the quasi-continuous filter belt crystallizer (QCFBC), a Peltier-element-driven, simplified experimental benchtop setup is validated in this work using a sucrose/water model substance system. It was shown that the operation conditions during the cooling crystallization on the continuously operated plant can be appropriately emulated; therefore, an actual operation of the entire mini-plant for characterization experiments is no longer necessary.

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Population balance modeling of unstirred cooling crystallization on an integrated belt filter

Cited by 5 publications

References 24 publications

From Lab to Pilot Scale: Commissioning of an Integrated Device for the Generation of Crystals

From Lab to Pilot Scale: Commissioning of an Integrated Device for the Generation of Crystals

Dynamic Modeling and Optimal Design Space Determination of Pharmaceutical Crystallization Processes: Realizing the Synergy between Off-the-Shelf Laboratory and Industrial Scale Data

Simplified Approach to Characterize the Cooling Crystallization in a Modular Mini-Plant

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