Ibrutinib Polymorphs: Crystallographic Study
Result description
In this paper, we present a comprehensive crystallographic study of Ibrutinib polymorphs and their behavior. Three neat polymorphs (A, B, and C) and a methanol solvate (F) were obtained and characterized. The structures of forms A, C, and F were solved from single-crystal diffraction data. Form B has only ever been prepared as a powder, and its structure solution has, so far, not been successful. Polymorph C is a desolvate of the methanol solvate F, and its structure was solved via the single-crystal to single-crystal transformation. The analysis of the solved structures revealed significant differences in the crystal packing of form A in comparison with the previously described Ibrutinib structures, enabling it to crystallize in a higher symmetry space group (monoclinic vs triclinic). The structures also revealed a high similarity between forms C and F, explaining their mutual transformability. To further analyze the solids, we performed DSC, long-term slurry transformations, intrinsic dissolution experiments, and DVS. FT-Raman spectroscopy was used for the preliminary characterization and fast distinction between the forms. We have also performed basic energy calculations to estimate the strength of the various present H-bonds. All methods confirmed the polymorph A to be the thermodynamically most stable form. © 2018 American Chemical Society.
Keywords
CLLFUTUREKINASELYMPHOMACHEMISTRYCRYSTALLIZATIONSALT DISPROPORTIONATIONDISAPPEARING POLYMORPHS
The result's identifiers
Result code in IS VaVaI
Alternative codes found
RIV/68378271:_____/18:00497273 RIV/60461373:22340/18:43916530 RIV/60461373:22810/18:43916530
Result on the web
DOI - Digital Object Identifier
Alternative languages
Result language
angličtina
Original language name
Ibrutinib Polymorphs: Crystallographic Study
Original language description
In this paper, we present a comprehensive crystallographic study of Ibrutinib polymorphs and their behavior. Three neat polymorphs (A, B, and C) and a methanol solvate (F) were obtained and characterized. The structures of forms A, C, and F were solved from single-crystal diffraction data. Form B has only ever been prepared as a powder, and its structure solution has, so far, not been successful. Polymorph C is a desolvate of the methanol solvate F, and its structure was solved via the single-crystal to single-crystal transformation. The analysis of the solved structures revealed significant differences in the crystal packing of form A in comparison with the previously described Ibrutinib structures, enabling it to crystallize in a higher symmetry space group (monoclinic vs triclinic). The structures also revealed a high similarity between forms C and F, explaining their mutual transformability. To further analyze the solids, we performed DSC, long-term slurry transformations, intrinsic dissolution experiments, and DVS. FT-Raman spectroscopy was used for the preliminary characterization and fast distinction between the forms. We have also performed basic energy calculations to estimate the strength of the various present H-bonds. All methods confirmed the polymorph A to be the thermodynamically most stable form. © 2018 American Chemical Society.
Czech name
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Czech description
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Classification
Type
Jimp - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
20401 - Chemical engineering (plants, products)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Crystal Growth & Design
ISSN
1528-7483
e-ISSN
—
Volume of the periodical
18
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
1315-1326
UT code for WoS article
000427203700010
EID of the result in the Scopus database
2-s2.0-85043261247
Basic information
Result type
Jimp - Article in a specialist periodical, which is included in the Web of Science database
OECD FORD
Chemical engineering (plants, products)
Year of implementation
2018