Ibrutinib Polymorphs: Crystallographic Study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22310%2F18%3A43916530" target="_blank" >RIV/60461373:22310/18:43916530 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378271:_____/18:00497273 RIV/60461373:22340/18:43916530 RIV/60461373:22810/18:43916530

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.cgd.7b00923" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.cgd.7b00923</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.cgd.7b00923" target="_blank" >10.1021/acs.cgd.7b00923</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ibrutinib Polymorphs: Crystallographic Study

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Ibrutinib Polymorphs: Crystallographic Study

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

20401 - Chemical engineering (plants, products)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Crystal Growth &amp; Design

ISSN

1528-7483

e-ISSN

—

Svazek periodika

18

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

1315-1326

Kód UT WoS článku

000427203700010

EID výsledku v databázi Scopus

2-s2.0-85043261247