Continuous reactive crystallization of pharmaceuticals using impinging jet mixers

Liu, Wen J.; Cai, Yong; Liu, Jing J.; Yang, Zhigang; Wang, Xue Z.

doi:10.1002/aic.15438

Cited by 24 publications

(12 citation statements)

References 35 publications

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“…Impinging jet mixer could shorten the mixing time, preventing crystal agglomeration and further reducing the product size distribution. Liu et al 67 used impinging jet mixers to produce sodium cefuroxime. The new designed process could produce crystals with a narrower particle size distribution and improved product stability.…”

Section: Crystal Growth and Designmentioning

confidence: 99%

Control of Crystal Properties in a Mixed-Suspension Mixed-Product Removal Crystallizer: General Methods and the Effects of Secondary Nucleation

Zhang¹,

Wang²,

Ulrich

et al. 2019

Crystal Growth & Design

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Continuous crystallization has gained growing interest in the pharmaceutical industry due to its high productivity and consistency of the product quality. Significant progress on the control of mixed-suspension mixed-product removal (MSMPR) product properties with the aspects of crystal size distribution, polymorphism, and crystal shape has been achieved. This review aims to summarize different property control methods and put forward new viewpoints on process control by applying a secondary nucleation mechanism. The review begins with a brief introduction to the characteristics and mechanisms of secondary nucleation, followed by an attempt to investigate the underlying phenomena involved in secondary nucleation. Then, the steadystate conditions of continuous crystallization from mathematical and mechanism analyses are discussed. Subsequently, the focus is on a variety of approaches that have been implemented in continuous crystallization processes to enable crystals to meet different critical quality attributes. Among them, by applying a secondary nucleation mechanism, new design strategies for crystal size and polymorph control in continuous crystallization are proposed. Furthermore, the possible relationship between the secondary nucleation threshold and crystal shape distribution is elaborated using a theoretical analysis and selecting supporting experimental evidence from the literature.

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Section: Crystal Growth and Designmentioning

confidence: 99%

Control of Crystal Properties in a Mixed-Suspension Mixed-Product Removal Crystallizer: General Methods and the Effects of Secondary Nucleation

Zhang¹,

Wang²,

Ulrich

et al. 2019

Crystal Growth & Design

View full text Add to dashboard Cite

show abstract

“…There are two main types of reactors commonly used for precipitation generation. One is the stirred reactor, 8 which has a large flux per unit time, but there is a dead zone in the stirring process 9 which makes the velocity field distribution inhomogeneous, 10 so the mixing effect is not ideal. 11 Moreover, differences in experimental conditions between batches will lead to differences in products, 12 especially when the reactor is scaled up.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Micro-/Nanohydroxyapatite Assisted by the Taylor–Couette Flow Reactor

Wang

Tao

2022

ACS Omega

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Hydroxyapatite (HAP) has received increasing attention as an essential chemical product with good biocompatibility and adsorption properties. Generally, amorphous calcium phosphate (ACP) was generated first in the reactor and transformed into HAP after a period of crystallization. In this work, a series of Taylor–Couette flow reactors with different inner diameters were designed to assist in synthesizing HAP micro-/nanocrystals. ACP was obtained in a Taylor–Couette flow reactor at Re = 247 and successfully transformed into needle-like HAP crystals with a length of about 200 nm and a uniform particle size distribution after crystallization transformation. The yield of a single reactor can reach 2.16 kg per day. The finite element analysis results and time–space diagram of flow pattern variation showed that the Taylor–Couette flow reactor could improve the mixing behavior and the flow field distribution. The Taylor–Couette flow reactor provides a valuable reference for synthesizing inorganic micro-/nanomaterials.

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“…Gas–liquid (G–L) reactive crystallization is a fundamental technology to produce advanced materials, which have been widely used in medicine, battery, electronic, and atomic energy industries. − The rapid generation of supersaturation during the G–L reactive crystallization made it difficult to control. , The micromixing of the reactant and transfer of crystallization components are both restrained by diffusion, , which requires a short diffusion path to ensure the reactant supply at the reactive interface and maintain stable nucleation procedures. Specifically, the uniform G–L interface is helpful to achieve sufficient diffusion and uniform supersaturation distribution and promote the controllable nucleation of crystals.…”

Section: Introductionmentioning

confidence: 99%

A Covalent Organic Framework Membrane with Homo Hierarchical Pores for Confined Reactive Crystallization

Jiang

Meng

et al. 2022

ACS Appl. Mater. Interfaces

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Gas–liquid (G–L) reactive crystallization is a major technology for advanced materials construction, which requires a short diffusion path on the interface to ensure the reactant supply and stable crystal nucleation under ultrahigh supersaturation. Herein, a covalent organic framework (COF) membrane with homo hierarchical pore structures was proposed as an effective interfacial material for the regulation of confined reactive crystallization. By combining the ordered nanopores of COFs and micropores of anodic aluminum oxide (AAO), the COF membrane simultaneously provided an excellent nanoscale diffusion–reaction regulation network as the molecular-level confined G–L reactive interface and adjustable submicrometer gas mass transfer channels. The highly selective construction of CaCO3 superstructures was then achieved. When the submicrometer primary pore size r p of the constructed COF membrane ranged from 120 to 1.6 nm, the diffusion mechanism of CO2 varied from viscous flow diffusion to Knudsen diffusion. The growth orientation of CaCO3 crystals was well confined to obtain spindle-shaped crystals with high selectivity. Meanwhile, the crystal selectivity factor (cube/sphere) increased from 0 to 3.53 under the low interfacial nuclear barrier. Thus, the COF membrane with coupled micro-nanostructures successfully screened the directional preparation conditions for diverse CaCO3 superstructures, which also paved a meaningful path for the functional application of COFs in accurate mass transfer control and confined chemical reactions.

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Continuous reactive crystallization of pharmaceuticals using impinging jet mixers

Cited by 24 publications

References 35 publications

Control of Crystal Properties in a Mixed-Suspension Mixed-Product Removal Crystallizer: General Methods and the Effects of Secondary Nucleation

Control of Crystal Properties in a Mixed-Suspension Mixed-Product Removal Crystallizer: General Methods and the Effects of Secondary Nucleation

Synthesis of Micro-/Nanohydroxyapatite Assisted by the Taylor–Couette Flow Reactor

A Covalent Organic Framework Membrane with Homo Hierarchical Pores for Confined Reactive Crystallization

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