Implementation of sonicated continuous plug flow crystallization technology for processing of acetylsalicylic acid reaction mixture

Tacsi, Kornélia; Stoffán, György; Pusztai, Éva; Nagy, Brigitta; Domokos, András; Szilágyi, Botond; Nagy, Zsombor Kristóf; Marosi, György; Pataki, Hajnalka

doi:10.1016/j.powtec.2022.117255

Cited by 8 publications

(5 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Continuous crystallization is a well-established research field with two basic operational implementations, which are the mixed suspension mixed product removal (MSMPR) crystallizers , and different tubular crystallizers (TC). − The assembling of more MSMPR units into a cascade crystallizer system or the connection of different types of continuous crystallizers − allows even more possibilities to control crystallization on its subprocess levels. The elevated performance of merging continuous and additive-controlled crystallization is demonstrated through the following examples from the literature.…”

Section: Introductionmentioning

confidence: 99%

Development of Continuous Additive-Controlled MSMPR Crystallization by DoE-Based Batch Experiments

Stoffán,

Lőrincz,

Pusztai

et al. 2024

Ind. Eng. Chem. Res.

Self Cite

View full text Add to dashboard Cite

Additive-controlled crystallization is a promising method to improve crystal morphology and produce solid drug particles with the desired technological and pharmacological properties. However, its adaptation to continuous operation is a hardly researched area. Accordingly, in this work, we aimed to come up with a methodology that provides the systematic and fast development of a continuous three-stage MSMPR cascade crystallizer. For that, a cooling crystallization of famotidine (FMT) from water, in the presence of a formulation additive, poly(vinylpyrrolidone) (PVP-K12), was developed. Process parameters with a significant impact on product quality and quantity were examined in batch mode through a 2 4−1 fractional factorial design for the implementation of additive-controlled continuous crystallization. These batch experiments represented one residence time of the continuous system. Based on the statistical analysis, the residence time (RT) had the highest effect on yield, while the polymer amount was critical from the product polymorphism, crystal size, and flowability points of view. The values of critical process parameters in continuous operation were fixed according to the batch results. Two continuous cooling crystallization experiments were carried out, one with 1.25 w/w FMT % PVP-K12 and one with no additive. A mixture of FMT polymorphs (Form A and Form B) crystallized without the additive through five residence times (>6.5 h) with 70.8% overall yield. On the other hand, the additive-controlled continuous experiment resulted pure and homogeneous Form A product with excellent flowability. The system could be operated for >6.5 h without clogging with a 71.1% overall yield and a 4-fold improvement in productivity compared to its batch equivalent.

show abstract

Section: Introductionmentioning

confidence: 99%

Development of Continuous Additive-Controlled MSMPR Crystallization by DoE-Based Batch Experiments

Stoffán,

Lőrincz,

Pusztai

et al. 2024

Ind. Eng. Chem. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite its many advantages, the application of ultrasound to crystallization is greatly limited by the lack of suitable acoustic equipment. , There are two commonly used types of acoustic equipment, i.e., direct immersion of an ultrasonic probe into a kettle crystallizer and immersion of a tubular crystallizer in an ultrasonic water bath. − , Nonetheless, for typical kettle crystallizers, the ultrasonic intensity is low in most regions away from the horn as the effective irradiation distance within the solution is restricted to just a few centimeters. , On the other hand, the latter type of crystallizer suffers from the dissipation of ultrasonic energy into the water bath. , Coupling the crystallizer and the ultrasonic generator as a whole device can effectively improve the utilization rate of the acoustic energy. Hussain et al constructed an efficient crystallizer by coupling a crystallization tube to an ultrasonic generator.…”

Section: Introductionmentioning

confidence: 99%

“…A reliable crystallizer should be developed to solve the problems of energy dissipation and thermal effect. Additionally, a systematic study of the sonocrystallization process in tubular crystallizers is necessary. ,, …”

Section: Introductionmentioning

confidence: 99%

“…25,26 On the other hand, the latter type of crystallizer suffers from the dissipation of ultrasonic energy into the water bath. 27,28 Coupling the crystallizer and the ultrasonic generator as a whole device can effectively improve the utilization rate of the acoustic energy. Hussain et al 4 constructed an efficient crystallizer by coupling a crystallization tube to an ultrasonic generator.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, a systematic study of the sonocrystallization process in tubular crystallizers is necessary. 8,27,29 In this work, a highly efficient ultrasonic tubular crystallizer was designed. Its vibration characteristics were simulated, and the sound power density was measured.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ultrasonic Enhanced Continuous Crystallization: Induction Time and Process Control

Zhao,

Yang,

Yao

et al. 2023

Ind. Eng. Chem. Res.

View full text Add to dashboard Cite

An ultrasound-assisted tube crystallization device was designed for the continuous antisolvent crystallization of acetylsalicylic acid. Both the COMSOL simulation and experimental characterization showed that the designed acoustic crystallizer exhibited high energy efficiency and excellent temperature control. The effects of ultrasonic power, ultrasonic action time, supersaturation degree, and ultrasonic excitation method on the crystallization process were investigated. Due to the intensification of fluid mixing and the introduction of cavitation bubbles as the heterogeneous nucleation sites, the crystallization was significantly enhanced. The induction time of the crystallization was shortened to several hundred milliseconds. The crystallization efficiency could be as high as 80% achieved within 0.46 s. The average particle size of the crystals ranged from 8.2 to 40.1 μm, with a span value of less than 1. Meanwhile, the pulse excitation method can further reduce energy consumption while maintaining the advantages of sonocrystallization. All of these results indicate a far better performance of the present crystallization device than conventional crystallizers, validating the effectiveness of ultrasound promotion. The results also provide insights into optimal operating conditions for ultrasonic crystallization.

show abstract

Assessments of the heat transfer performance of a novel continuous oscillatory baffled crystallizer via two-fluid model

Huang

Zhang

et al. 2023

Chemical Engineering Science

View full text Add to dashboard Cite

Implementation of sonicated continuous plug flow crystallization technology for processing of acetylsalicylic acid reaction mixture

Cited by 8 publications

References 68 publications

Development of Continuous Additive-Controlled MSMPR Crystallization by DoE-Based Batch Experiments

Development of Continuous Additive-Controlled MSMPR Crystallization by DoE-Based Batch Experiments

Ultrasonic Enhanced Continuous Crystallization: Induction Time and Process Control

Assessments of the heat transfer performance of a novel continuous oscillatory baffled crystallizer via two-fluid model

Contact Info

Product

Resources

About