Comprehensive sensitivity analysis and process risk assessment of large scale pharmaceutical crystallization processes

Öner, Merve; Stocks, Stuart M.; Sin, Gürkan

doi:10.1016/j.compchemeng.2020.106746

Cited by 15 publications

(13 citation statements)

References 50 publications

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“…Lowering crystal growth rate may cause increment in nucleation rate which causes the increased in concentration, thus increasing supersaturation level . This is also known as supersaturation consumption (Rasmuson, 266 Effects of Nucleation and Crystal Growth Rates on Crystal Size Distribution for Seeded Batch Potash Alum Crystallization Process other issues (Trampuž et al, 2020, Öner et al, 2020, Adnan et al, 2019, Fysikopoulos et al, 2019, Seki and Su, 2015. These results presented an insight into developing a unified final CSD with minimum amounts of fine crystals by lowering both nucleation and crystal growth rates.…”

Section: Effects Of Crystal Growth Ratementioning

confidence: 95%

“…Adnan and N. A. F. A. Samad 259 Su, 2015). Production specifications such as specified size, purity, crystal habit, and crystal size distribution (CSD) of the final crystal product are essential for the crystallization process (Trampuž et al, 2021, Trampuž et al, 2020, Öner et al, 2020. This has led to the establishment of optimization strategies for producing high-quality final products, especially in terms of CSD, to achieve the desired crystal target.…”

Section: Considerablementioning

confidence: 99%

“…Due to this, along with the grown seed crystals stimulated by the high crystal growth rate, fine crystals are also produced significantly, which is induced by the high nucleation rate. High production of fine crystals may cause the problem in later processing, such as long operational time for filtration and drying of crystals (Öner et al, 2020, Adnan et al, 2019, Seki and Su, 2015, as well as encrustation on internal surfaces of equipment (Acevedo et al, 2019, Seki and Su, 2015.…”

Section: Considerablementioning

confidence: 99%

“…The classical approach is by implementing the one-factor-at-a-time (OFAT) method. OFAT enables a less time-consuming approach where useful sensitivity index estimation may still be obtained (Morio, 2011) (Wang et al, 2021, Öner et al, 2020, Fysikopoulos et al, 2019, Fysikopoulos et al, 2017.…”

Section: Considerablementioning

confidence: 99%

See 3 more Smart Citations

Effects of Nucleation and Crystal Growth Rates on Crystal Size Distribution for Seeded Batch Potash Alum Crystallization Process

Adnan

Samad

2022

ASEAN J. Chem. Eng.

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The driving force of the cooling crystallization process is supersaturation, where the supersaturation level during the crystallization process is crucial to grow the crystal sufficiently. Nucleation and crystal growth rates are two concurrent phenomena occurring during crystallization. Both are supersaturation functions that determine the growth of seed crystals and the formation of fine crystals. Trade-offs between nucleation and crystal growth are essential for achieving the large size of seed crystals with the minimum number of fine crystals. Thus, the objective of this study is to analyze the effects of nucleation and crystal growth rates on final product quality, which is crystal size distribution (CSD). Modeling of the crystallization process using a potash alum case study is highlighted and simulated using Matlab software. Then, the effects of nucleation rate, crystal growth rate, and both nucleation and crystal growth rates on CSD are evaluated using local sensitivity analysis based on the one-factor-at-a-time (OFAT) method. Based on simulation results for all strategies, a low combined rate delivers the best performance of the final CSD compared to others. Its primary peak has a mean crystal size of 455 µm with 0.0078 m3/m volume distribution. This means that the grown seed crystals are large with high volume distribution compared to the nominal strategy, which is at the mean crystal size of 415 µm and 0.00434 m3/m. Meanwhile, the secondary peak has the mean crystal size of 65 µm, 0.00028 m3/m in volume distribution. This corroborates the least number of fine crystals at the considerably small size compared to nominal’s (0.00151 m3/m, 35 µm). Overall, the low nucleation and crystal growth rates strategy provides useful insights into designing temperature profiles during the linear cooling crystallization process, whereby achievable supersaturation levels in obtaining large crystals with fewer crystal fines are provided via simulation.

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Section: Effects Of Crystal Growth Ratementioning

confidence: 95%

Section: Considerablementioning

confidence: 99%

Section: Considerablementioning

confidence: 99%

Section: Considerablementioning

confidence: 99%

See 2 more Smart Citations

Effects of Nucleation and Crystal Growth Rates on Crystal Size Distribution for Seeded Batch Potash Alum Crystallization Process

Adnan

Samad

2022

ASEAN J. Chem. Eng.

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“…ESCs significantly contribute to the sustainment of many industrial areas, such as biomass [5], food [6], oil and gas [7,8], chemistry [9], and sustainable and renewable energy [10][11][12]. For this, ESCs must offer enhanced flexibility, innovative connectivity and communication to guarantee an orderly and healthy supply management environment to improve the way the energy industrial world copes with changes and adapts to risks [8,9,[13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

A Simulation-Based Multi-Objective Optimization Framework for the Production Planning in Energy Supply Chains

2021

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The work presents a simulation-based Multi-Objective Optimization (MOO) framework for efficient production planning in Energy Supply Chains (ESCs). An Agent-based Model (ABM) that is more comprehensive than others adopted in the literature is developed to simulate the agent’s uncertain behaviors and the transaction processes stochastically occurring in dynamically changing ESC structures. These are important realistic characteristics that are rarely considered. The simulation is embedded into a Non-dominated Sorting Genetic Algorithm (NSGA-II)-based optimization scheme to identify the Pareto solutions for which the ESC total profit is maximized and the disequilibrium among its agent’s profits is minimized, while uncertainty is accounted for by Monte Carlo (MC) sampling. An oil and gas ESC model with five layers is considered to show the proposed framework and its capability of enabling efficient management of the ESC sustained production while considering the agent’s uncertain interactions and the dynamically changing structure.

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A generalized zoning framework for development of CFD‐based reduced‐order compartment models

Liu

Wilhite

2023

AIChE Journal

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While computational fluid dynamics (CFD)-based compartment models have gained popularity as a cost-effective alternative to full CFD modeling of complex mixing systems, model development involves significant trial-and-error efforts. This work presents a generalized zoning framework for the streamlined development of CFDbased compartment models with detailed characterization of the reduced-order representation of the flow physics. With a stirred tank as an illustrative case, reducedorder model for species transport and heat transfer with turbulent flow is derived, followed by introducing the generalized zoning framework to demonstrate how a reduced-order compartment model can be constructed based on a simplified CFD simulation. A test case of mixing two miscible thermal fluids is used to evaluate the CFD-based compartment model. The results demonstrate that the proposed zoning framework exhibits an accurate representation of the CFD simulation of hydrodynamics and demonstrates capabilities of capturing species and heat transfer in turbulent flow systems with complex geometric configurations.

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Comprehensive sensitivity analysis and process risk assessment of large scale pharmaceutical crystallization processes

Cited by 15 publications

References 50 publications

Effects of Nucleation and Crystal Growth Rates on Crystal Size Distribution for Seeded Batch Potash Alum Crystallization Process

Effects of Nucleation and Crystal Growth Rates on Crystal Size Distribution for Seeded Batch Potash Alum Crystallization Process

A Simulation-Based Multi-Objective Optimization Framework for the Production Planning in Energy Supply Chains

A generalized zoning framework for development of CFD‐based reduced‐order compartment models

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