A general method for cultivating single crystals from melt microdroplets

Xiao, Ou; Li, Xizhen; Rong, Haowei; Yu, Lian; Lü, Ming

doi:10.1039/d0cc03157g

Cited by 53 publications

(69 citation statements)

References 18 publications

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“…Polarized light microscope combined with hot stage can also be used to obtain highquality single crystals [35,36]. For instance, high-quality single crystals of the metastable form II of griseofulvin, was obtained from the melt under a polarized light microscope equipped with a hot stage [35].…”

Section: Combination Of Polarized Light Microscope and Hot Stagementioning

confidence: 99%

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

Wang

Cheng

et al. 2021

Crystals

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The amorphous form of a drug usually exhibits higher solubility, faster dissolution rate, and improved oral bioavailability in comparison to its crystalline forms. However, the amorphous forms are thermodynamically unstable and tend to transform into a more stable crystalline form, thus losing their advantages. In order to investigate and suppress the crystallization, it is vital to closely monitor the drug solids during the preparation, storage, and application processes. A list of advanced techniques—including optical microscopy, surface grating decay, solid-state nuclear magnetic resonance, broadband dielectric spectroscopy—have been applied to characterize the physicochemical properties of amorphous pharmaceutical solids, to provide in-depth understanding on the crystallization mechanism. This review briefly summarizes these characterization techniques and highlights their recent advances, so as to provide an up-to-date reference to the available tools in the development of amorphous drugs.

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Section: Combination Of Polarized Light Microscope and Hot Stagementioning

confidence: 99%

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

Wang

Cheng

et al. 2021

Crystals

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“…Melt crystallization has been an effective method of late for discovering new polymorphs. [18][19][20][21][22][23][24] LLA, however, when melted in sealed glass tubes and then quenched at 25°C…”

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confidence: 99%

Ambient l-lactic acid crystal polymorphism

Yang

Reiter

et al. 2021

CrystEngComm

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“…Recently, we developed a general method for rapidly growing single crystals from melt microdroplets. [12] This strategy highly facilitates the structure determination of polymorphs crystallized from the melt. [3,13] Single-crystal X-ray diffraction (SCXRD), the main workhorse in structural chemistry, requires good-sized crystals (usually larger than 50 μm in each dimension for laboratory diffractometers and 5-10 μm in each dimension for strong synchrotron radiation [14] ) of sufficient quality.…”

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confidence: 99%

“…This led us to ask, do the two crystallization methods of δ-IDM produce different polymorphs? In this work, we performed microdroplet melt crystallization [12] for single crystal cultivation of both melt-crystallized δ-IDM (melt δ-IDM) and solution-crystallized δ-IDM (solution δ-IDM ) and applied 3D ED for structure elucidation of both phases to correct this 47-year-old misunderstanding.…”

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confidence: 99%

“…Single crystals of melt and solution δ-IDM were cultivated from supercooled IDM by microdroplet melt crystallization. [12] Single crystals of melt δ-IDM are ribbons (Figures 3a and S4) and those of solution δ-IDM are needles (Figures 3d and S4). Both crystals exhibit one-dimensional growth and are too thin for sufficient X-ray crystallographyeven the third-generation synchrotron radiation source.…”

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A 47-year-old misunderstanding: Indomethacin Polymorph δ revealed to be two plastically bendable crystal forms by 3D electron diffraction

Lightowler

Xiao

et al. 2021

Preprint

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Indomethacin is a clinically classical non-steroidal anti-inflammatory drug that has been marketed since 1965. The third polymorph, Form δ, was discovered by both melt and solution crystallization in 1974. δ-indomethacin cannot be cultivated as a large single crystal suitable for X-ray crystallography and, therefore, its crystal structure has not yet been determined. Here, we report the structure elucidation of δ-indomethacin by 3D electron diffraction and reveal the truth that melt-crystallized and solution-crystallized δ-indomethacin are in fact two polymorphs with different crystal structures. Intriguingly, both structures display plastic flexibility based on a slippage mechanism, making indomethacin the first drug to have two plastic polymorphs. This discovery and correction of a 47-year-old misunderstanding signify that 3D electron diffraction has become a powerful tool for polymorphic structural studies.

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A general method for cultivating single crystals from melt microdroplets

Abstract: The cultivation of single crystals from solution is usually a time-consuming trial-and-error game. Here, we report a general strategy for rapidly cultivating single crystals from melt microdroplets within tens of...

Cited by 53 publications

References 18 publications

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

Recent Advances in the Application of Characterization Techniques for Studying Physical Stability of Amorphous Pharmaceutical Solids

Ambient l-lactic acid crystal polymorphism

A 47-year-old misunderstanding: Indomethacin Polymorph δ revealed to be two plastically bendable crystal forms by 3D electron diffraction

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