A flow-free droplet-based device for high throughput polymorphic crystallization

Yang, Shih-Mo; Zhang, David; Chen, Wang; Chen, Shih‐Chi

doi:10.1039/c5lc00448a

Cited by 18 publications

(18 citation statements)

References 24 publications

(36 reference statements)

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“…The distinct prismatic and triangular pyramid forms can be readily identified as α-, and γ-polymorphs of glycine, respectively, in accordance with previous work. 36 The polymorphic nature of the SAs was determined by XRD to be αglycine. When the ratio of glycerol to water in the outer continuous phase rose to 5:1, γ-form disappeared and a nearly equal proportion of α-form and SAs habits were observed in QDEs.…”

Section: Control Of Glycine Polymorph Crystallization By Tuningmentioning

confidence: 99%

Static Quasi-Double Emulsions as Programmable Microcrystallizers for Controllable Polymorphic Crystallization

Xiong

Liu

et al. 2022

Preprint

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Controlling crystal polymorphism is critical in many fields such as pharmaceuticals, biomineralization, and catalysis. However, it is challenging for conventional batch crystallization approaches to effectively control the polymorphism of obtained crystals. In this work, we introduce a novel approach for controlling polymorphic crystallization by using quasi-double-emulsions (QDEs) as programmable microcrystallizers. The QDEs utilize a thin oil layer to separate aqueous droplets trapped in a high-density microwell array from the continuous aqueous phase, forming a large number of water-oil-water (W/O/W) structures similar to double emulsions. Benefitting from the semi-permeability of its middle oil film, the QDEs platform can facilely and flexibly vary the supersaturation rate and solvent composition of its inner aqueous phase (IAP) via changing its outer aqueous phase (OAP). Such variations can tune the kinetics of crystallization in the IAP, thus achieving highly controlled polymorphic crystallization and obtaining desired crystal polymorphs. In a proof-of-concept application, we demonstrated the convenience and versatility of the QDE platform by applying it for regulating the polymorph of glycine. Compared to traditional crystallizers, the QDEs platform provides more controllability and flexibility in polymorphic crystallization, being a powerful tool for solid form screening in pharmaceutical, fine chemicals, and food industries.

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Section: Control Of Glycine Polymorph Crystallization By Tuningmentioning

confidence: 99%

Static Quasi-Double Emulsions as Programmable Microcrystallizers for Controllable Polymorphic Crystallization

Xiong

Liu

et al. 2022

Preprint

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“…Thus, confinement may affect phase stability. Such an effect is expected to be at work also in droplet protein crystallization [12,13], confined polyelectrolyte solutions [14] and polymer blends [15], and compartmentalization in biological cells [16][17][18]. Such a universal importance of phase stability under confinement, encountered in diverse disciplines, necessitates the extension of thermodynamic phase stability, developed so far in macroscopic systems [19][20][21][22][23], to solution mixtures confined in small systems.…”

Section: Introductionmentioning

confidence: 99%

Phase stability condition and liquid–liquid phase separation under mesoscale confinement

Shimizu

Matubayasi

2021

Physica A: Statistical Mechanics and its Applications

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Here we establish the thermodynamic phase stability condition under mesoscale confinement, which is essential in elucidating how the confinement of solutions inside a droplet, cell or liposome may influence phase separation. To clarify how phase stability is affected by external conditions, a formal analogy between the partially open ensemble and mesoscopic system will be exploited, through which the nonnegligible role of the system boundary will be identified as the crucial difference from the macroscopic stability condition. The thermodynamic stability condition extended for mesoscale is shown to involve several different orders of magnitude that are all considered to be O(1) at a macroscopic limit. Phase instability in mesoscale is shown to ensue when the difference between self-association (relative self-fluctuation of particle number) and mutual association (relative number correlation between different species) reaches the mesoscopic order of magnitude, in contrast to the divergence of particle number fluctuation

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“…The pharmaceutical industry also requires high quality products with a monodisperse crystal size distribution (CSD) and a low aspect ratio morphology (Christian et al, 2000;Yang et al, 2015). However, in reaction crystallization, the dispersion coefficient tends to be large, and crystal particles with a wide CSD are often precipitated (Mikami et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Control of Reaction Crystallization of Organic Compounds Using the Supersaturation Profile

Sato

Seki

Takiyama

2019

J. Chem. Eng. Japan / JCEJ

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Neutralization reaction crystallization is useful for manufacturing drugs that require high bioavailability (i.e., high solubility). Because drug crystals must be of high quality, with the optimal form and particle size, the development of procedures that can produce high quality crystals by reaction crystallization is important. In cooling crystallization, analysis of the supersaturation pro le (SSP) is an e ective way to improve the crystal quality. SSP analysis is also important in reaction crystallization. However, the changes in the operation parameters (e.g., pH) necessary for crystallization strongly depend on the deposition of the crystals. Thus, solution pH also changes with deposition of the crystals. The purpose of this study is to propose an optimal crystallization point for the improvement of crystal quality through SSP analysis in reaction crystallization. The experimental system involved the reaction of hydrochloric acid and L-arginine to crystallize L-arginine hydrochloride monohydrate. The SSP was computed using HPLC and a pH meter. The relationship among the amount of feed added, crystal size distribution (CSD), and the crystal morphology was investigated through SSP analysis. Control of minute crystals was found to be crucial for CSD improvement. Moreover, operation at a neutral pH and the use of seed crystals were found to e ectively inhibit the formation of minute crystals. Furthermore, operation at basic pH effectively produced good crystal morphology. Finally, using these results to modulate the addition technique in the reaction crystallization process, quality crystals with the desired CSD and morphology have been produced.

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A flow-free droplet-based device for high throughput polymorphic crystallization

Cited by 18 publications

References 24 publications

Static Quasi-Double Emulsions as Programmable Microcrystallizers for Controllable Polymorphic Crystallization

Static Quasi-Double Emulsions as Programmable Microcrystallizers for Controllable Polymorphic Crystallization

Phase stability condition and liquid–liquid phase separation under mesoscale confinement

Control of Reaction Crystallization of Organic Compounds Using the Supersaturation Profile

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