Enhancing pharmaceutical crystallization in a flow crystallizer with ultrasound: Anti-solvent crystallization

Hussain, Mohammed Noorul; Jordens, Jeroen; John, Jinu Joseph; Braeken, Leen; Gerven, Tom Van

doi:10.1016/j.ultsonch.2019.104743

Cited by 41 publications

(71 citation statements)

References 30 publications

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“…where value is a combination of the temperature of the upstream process, and the heat of mixing between the water and the ethanol. 19,25,26 In our experiments, the population density and temperature in boundary conditions are, n f eed = 0 #•m −3 •s −1 , and T in = 298 K.…”

Section: Boundary and Initial Conditionsmentioning

confidence: 99%

“…The high fidelity crystallization model of aspirin has been validated previously, and it could capture the sonicated lab-scale continuous crystal production, including all heat transfer phenomena that occur and might affect the process. 19,26 The overall objective of this article is to develop and validate a CFD model for the ultrasound-assisted continuous antisolvent crystallization of aspirin for scale-up. Diverging from previous mathematical models for the continuous antisolvent crystallization of aspirin, 26 this article presents the first tubular crystallizer model that (1) considers a validated acoustic field in the reactor generated by the ultrasound transducer, (2) takes into consideration the proper fluid flow model (laminar or turbulent with micromixing), (3) uses validated expressions of solubility, nucleation, and growth rates, and (4) predicts the crystal growth in the presence of ultrasound in a scaled-up reactor.…”

Section: Introductionmentioning

confidence: 99%

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Theoretical Study of the Scalability of a Sonicated Continuous Crystallizer for the Production of Aspirin

Savvopoulos

Hussain

Gerven

et al. 2020

Ind. Eng. Chem. Res.

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Ultrasound is frequently applied in crystallization to enhance nucleation and achieve crystal sizes within a narrow range. In this work, a mathematical model is developed which couples the acoustic effect of ultrasound on the antisolvent crystallization of aspirin with the flow hydrodynamics and associated micromixing. In the first step, a qualitatively validated 3D acoustic simulation of the crystallizer is used to understand the acoustic field in the reactor. Following this an assessment of various flow and micromixing models is carried out using a 3D CFD model which is compared to a previously validated 1D model. The identified models successfully capture the acoustic field and predict the crystal size and the crystals' coefficient of variation in experimental studies. The proposed model offers a practical platform that can be applied to experiments for improving the design of continuous crystallizers, as the model has

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Section: Boundary and Initial Conditionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Theoretical Study of the Scalability of a Sonicated Continuous Crystallizer for the Production of Aspirin

Savvopoulos

Hussain

Gerven

et al. 2020

Ind. Eng. Chem. Res.

View full text Add to dashboard Cite

show abstract

“…No crystallization was noticed in silent conditions as the induction time is much larger than the residence time. 3 To ensure a steady state, the combined flow of solution and antisolvent is allowed to run for 20 residence times in the crystallizer. Only after this, ultrasound is applied.…”

Section: Crystallization Proceduresmentioning

confidence: 99%

A Mathematical Model of the Ultrasound-Assisted Continuous Tubular Crystallization of Aspirin

Savvopoulos

Hussain

Jordens

et al. 2019

Crystal Growth & Design

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Ultrasound-assisted nucleation is a promising method of controlling the crystal length within a narrow range in antisolvent crystallization. This article proposes novel model equations representing crystal nucleation and growth under ultrasound application in the antisolvent system of ethanol (solvent), water (antisolvent), and aspirin (pharmaceutical ingredient). The model considers the enhancement of nucleation by ultrasound, and also accounts for the heat generated from both the application of ultrasound and the mixing of solvent and antisolvent. We further employ a global sensitivity analysis to determine the parameters that have the most significant impact on model outputs before validating multiple experimental case studies that represent crystal growth for different antisolvent contents and initial supersaturation ratios. The model successfully captures the effect of the ultrasound, which is a function of temperature and supersaturation ratio, and has a strong impact on the refinement and the

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“…In the pharmaceutical sector, sonocrystallization has attracted profound attention. Hussain et al elucidated how ultrasound benefited the crystallisation of ASA-Asprin in terms of reduced induction time due to accelerated nucleation, although conditions involved low saturation levels [33] . Further Isari et al, in their studies on sono-photolytic degradation of pharmaceutical wastewater, exemplified the synergistic effect caused when ultrasound is coupled with the conventional techniques [34] .…”

Section: Introductionmentioning

confidence: 99%

A review on recent advances in hydrogen energy, fuel cell, biofuel and fuel refining via ultrasound process intensification

Zore

Yedire

Pandi

et al. 2021

Ultrasonics Sonochemistry

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Highlights A detailed review of ultrasound enabled mechanism and its disparate applications have been presented. Emphasis is made on the sonochemical routes for hydrogen production and their advantages. Recent research studies on the synthesis of materials for hydrogen storage have been reported. Sonochemistry relevance in the fuel cell, biofuel technology and fuel refining have been discussed.

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Enhancing pharmaceutical crystallization in a flow crystallizer with ultrasound: Anti-solvent crystallization

Cited by 41 publications

References 30 publications

Theoretical Study of the Scalability of a Sonicated Continuous Crystallizer for the Production of Aspirin

Theoretical Study of the Scalability of a Sonicated Continuous Crystallizer for the Production of Aspirin

A Mathematical Model of the Ultrasound-Assisted Continuous Tubular Crystallization of Aspirin

A review on recent advances in hydrogen energy, fuel cell, biofuel and fuel refining via ultrasound process intensification

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