Continuous Cocrystallization of Benzoic Acid and Isonicotinamide by Mixing-Induced Supersaturation: Exploring Opportunities between Reactive and Antisolvent Crystallization Concepts

Svoboda, V.; MacFhionnghaile, Pól; McGinty, John; Connor, L. E.; Oswald, Iain D. H.; Šefčı́k, Ján

doi:10.1021/acs.cgd.6b01866

Cited by 30 publications

(33 citation statements)

References 28 publications

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“…In recent years, researchers have focused on improving the mixing efficiency by using various feed modes, the antisolvent‐solution contact approach, additional physical fields (electric, magnetic, etc. ), and novel feeding devices and crystallizers . However, because antisolvent transfer is based on the droplet or capillary mixing approach, the fundamental mixing mechanism is still limited by the mixing devices with a millimeter or submillimeter scale (10 −4 ‐10 −3 m).…”

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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“…Therefore, regulatory bodies, such as the FDA, proposed continuous processing and manufacturing, thus discouraging batch production. This implementation can satisfy flexible market demands, reduce operational complexities and interruptions ( 46 ). In the last decade, a combination of increased pressure from regulating bodies and advances in our understanding of ASDs has integrated HME as an essential manufacturing process in the pharmaceutical industry ( 47 ).…”

Section: Hot-melt Extrusionmentioning

confidence: 99%

Innovations in Thermal Processing: Hot-Melt Extrusion and KinetiSol® Dispersing

Tan

Davis

Miller³

et al. 2020

AAPS PharmSciTech

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Thermal processing has gained much interest in the pharmaceutical industry, particularly for the enhancement of solubility, bioavailability, and dissolution of active pharmaceutical ingredients (APIs) with poor aqueous solubility. Formulation scientists have developed various techniques which may include physical and chemical modifications to achieve solubility enhancement. One of the most commonly used methods for solubility enhancement is through the use of amorphous solid dispersions (ASDs). Examples of commercialized ASDs include Kaletra®, Kalydeco®, and Onmel®. Various technologies produce ASDs; some of the approaches, such as spray-drying, solvent evaporation, and lyophilization, involve the use of solvents, whereas thermal approaches often do not require solvents. Processes that do not require solvents are usually preferred, as some solvents may induce toxicity due to residual solvents and are often considered to be damaging to the environment. The purpose of this review is to provide an update on recent innovations reported for using hot-melt extrusion and KinetiSol® Dispersing technologies to formulate poorly water-soluble APIs in amorphous solid dispersions. We will address development challenges for poorly water-soluble APIs and how these two processes meet these challenges.

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“…A concentric mixing device 42 (Fig. 2) , modified for X-ray transparency, with a field-of-view is large enough to visualize the processes taking place in the mixing zone of the crystallizer, in real time, was developed.…”

Section: Flow Cellmentioning

confidence: 99%

“…The anti-solvent was delivered from either ends of the cross-piece as shown in Figure 1a to generate a uniform flow and aid mixing. 42 The inner tube was not perfectly centered due to gravitational sag. Gear pumps (Tuthill DGS.11EEET2NN00000 coupled with Dunkermotoren motor BG 45X30 SI, 24V) and flow meters (Bronkhorst, mini cori-flow M14) were used to regulate the flows.…”

Section: Flow Cellmentioning

confidence: 99%

Time-Resolved X-ray Phase-Contrast Imaging (XPCI) of Nucleation and Crystal Growth in the Anti-Solvent Crystallization of Lovastatin

Das¹,

Pallipurath

Leng³

et al. 2020

Preprint

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<p>X-ray phase contrast imaging (XPCI) of anti-solvent crystallization of lovastatin from an acetone/water solution was carried out in a concentric flow mixing device, using water as the anti-solvent. Spinodal decomposition of the solution is observed to give rise to ‘oiled out’ phases that undergo heterogeneous nucleation at the interface with the flowing solution. Heterogeneous nucleation is also observed on the walls of the reactor walls in the form of what appears to be Stranski–Krastanov growth of plate-like crystals. XPCI together with Eulerian video magnification forms a powerful tool for the spatio-temporal analysis, revealing mechanistic details of a non-equilibrium process such as anti-solvent crystallization.</p>

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Continuous Cocrystallization of Benzoic Acid and Isonicotinamide by Mixing-Induced Supersaturation: Exploring Opportunities between Reactive and Antisolvent Crystallization Concepts

Cited by 30 publications

References 28 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

Innovations in Thermal Processing: Hot-Melt Extrusion and KinetiSol® Dispersing

Time-Resolved X-ray Phase-Contrast Imaging (XPCI) of Nucleation and Crystal Growth in the Anti-Solvent Crystallization of Lovastatin

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