Hydrodynamic modeling of porous hollow fiber anti-solvent crystallizer for continuous production of drug crystals

Chen, Dengyue; Wang, Bing; Sirkar, Kamalesh K.

doi:10.1016/j.memsci.2018.03.046

Cited by 20 publications

(12 citation statements)

References 21 publications

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“…The droplet surface area is the limitation, and the diffusion resistance is high . In recent years, a porous membrane (with a 0.2 μm pore size)‐assisted crystallization device and a relevant computational fluid dynamic model‐based method were developed to realize continuous drug manufacturing and predict both the hydrodynamic conditions and mixing effectiveness. These results exhibit significant advantages in terms of mixing and process control, which shed light on the further application of membrane technology in continuous crystallization process control.…”

Section: Introductionmentioning

confidence: 99%

A novel hollow fiber membrane‐assisted antisolvent crystallization for enhanced mass transfer process control

et al. 2018

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Herein, a novel hollow fiber membrane‐assisted antisolvent crystallization (MAAC) was proposed to enhance the mass transfer control over the antisolvent crystallization. A polyethersulfone membrane module was introduced as the key device for antisolvent transfer and solution mixing. An antisolvent liquid film layer was formed on the membrane surface and mixed with the solution. The liquid film also prevented the membrane from directly contacting with crystallization solution. By controlling both the shell side flow velocity and the antisolvent transfer, the antisolvent permeation rate achieved sensitive, stable, and accurate control during long‐term and repeated utilization. The interfacial mass transfer rate of MAAC was 0.66 mg cm−2 s−1, which was only 1/50 that of conventional droplet antisolvent crystallization. MAAC also provided crystal products with better morphologies and narrower size distributions than the conventional process. The stable performances of MAAC in terms of its accurate antisolvent mass transfer and antifouling capabilities were also highlighted. © 2018 American Institute of Chemical Engineers AIChE J, 65: 734–744, 2019

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Section: Introductionmentioning

confidence: 99%

A novel hollow fiber membrane‐assisted antisolvent crystallization for enhanced mass transfer process control

et al. 2018

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“…Indeed, the physical properties, i.e. porous structure, and chemical nature of the membrane surface control the mass transfer rate of components and provide at the same time the micro-nano environment for crystal nucleation and growth [22][23][24][25]. The use of microporous hydrophobic supports covered with an hydrophilic hydrogel layer allows the production of protein crystals with improved diffraction properties due to the convection-free environment of the gel [26].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Protein Crystallization on Nafion Membranes Modified by Low-Cost Surface Patterning Techniques

Polino

Portugal

Tiggelaar³

et al. 2020

Crystal Growth & Design

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In this work, the influence of surface topography on protein crystallization over Nafion® is investigated. Two types of Nafion® based membranes were modified by soft lithographic techniques in order to create different topographies at the micro and nano scale and subsequently tested. From the analysis of the induction time, nucleation and crystal growth rate of Trypsin from Bovine Pancreas, all the patterned Nafion® based membranes show an enhanced nucleation and crystal growth. To provide additional insight to the experimental observations, the wettability properties of the prepared samples and the ratio of the Gibbs free energy of heterogeneous nucleation to homogeneous nucleation were evaluated. The crystallization outcome results from the combined effect of both, the structural and chemical properties of the nucleant Nafion® surface.

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“…This indicated the possibility of achieving the goal of drug nanocrystals through control of the nucleation, crystal-growing conditions, as well as device hydrodynamic majorization. 24 However, this PHFAC process for nanocrystal production was carried out for a short time period of less than 1 min. 25 One cannot claim this process as continuous unless such a process can be demonstrated to operate over an extended period of time without any change.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the PHFAC module and the HFM technique were applied for developing polymer-coated silica particles in submicron- and nanoscale as well, using a suspension of silica particles of appropriate dimensions. This indicated the possibility of achieving the goal of drug nanocrystals through control of the nucleation, crystal-growing conditions, as well as device hydrodynamic majorization …”

Section: Introductionmentioning

confidence: 99%

An Extended Duration Operation for Porous Hollow Fiber-Based Antisolvent Crystallization

Wang

Liu

et al. 2019

Ind. Eng. Chem. Res.

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Poor aqueous solubility of numerous active pharmaceutical ingredients has raised considerable concern about the bioavailability of drugs. A porous hollow fiber antisolvent crystallization (PHFAC) device was designed to continuously produce drug nanocrystals under ambient conditions. The drug solution pumped into the shell side of the module encountered jets of antisolvent deionized water from tiny pores on the hollow fiber walls inducing a high degree of supersaturation as well as crystallization of the obtained nanoparticles. To study the effect of duration of operation for the PHFAC module and the stability of the nanocrystal production, a larger-scale and a smaller-scale module were designed to compare the nanocrystals in a 60 min long experiment. The characterized results showed that the nanocrystals were stable in size and morphology, and the nanocrystals produced by the larger-scale module presented no difference from those of the small-scale module. Meanwhile, the drug nanoparticles remained unchanged for the 28 days during repeated production, indicating excellent stability. It appears possible that the experiment could be scaled up to bring the application to industrial practice.

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Hydrodynamic modeling of porous hollow fiber anti-solvent crystallizer for continuous production of drug crystals

Cited by 20 publications

References 21 publications

A novel hollow fiber membrane‐assisted antisolvent crystallization for enhanced mass transfer process control

A novel hollow fiber membrane‐assisted antisolvent crystallization for enhanced mass transfer process control

Enhanced Protein Crystallization on Nafion Membranes Modified by Low-Cost Surface Patterning Techniques

An Extended Duration Operation for Porous Hollow Fiber-Based Antisolvent Crystallization

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