Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions

Autores
Gaztañaga, Pablo Ernesto; Baggio, Ricardo Fortunato; Vega, Daniel Roberto
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Crystallographic, thermal and stability analyses are presented of three different anhydrated forms of bendamustine hydro­chloride [(I), (III) and (IV)] and a fourth, monohydrated one (II). Since form (I) presents the higher melting point and the higher heat of fusion, according to the 'heat of fusion' rule it should be the most stable in thermodynamic terms [Burger & Ramberger (1979). Mikrochim. Acta, 72, 259-271], though it is unstable in high-humidity conditions. The monohydrate structure (II), in turn, dehydrates by heating and topotactically transform into anhydrate (III). This latter form appears as less stable than anhydrate (I), to which it is linked via a monotropic relationship. For these three different forms, the crystal structure has been determined by single crystal X-ray diffraction. The crystal structures and molecular conformations of forms (II) and (III) are quite similar, as expected from the topotactic transformation linking them; furthermore, under high-humidity conditions, form (III) shows changes compatible with a transformation into form (II) within 24 h. The crystal structure of form (I) is different from the other two. The remaining polymorphic form (IV) could only be obtained as a powder, from which its crystalline structure could not be determined. The relative thermodynamic stability of the different crystalline forms was determined by differential scanning calorimetry and thermogravimetrical studies, and their stability under different humidity conditions analysed.
Fil: Gaztañaga, Pablo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Fil: Baggio, Ricardo Fortunato. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina
Fil: Vega, Daniel Roberto. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Materia
BENDAMUSTINE HYDROCHLORIDE
CRYSTAL STRUCTURE
POLYMORPHISM
SINGLE-CRYSTAL X-RAY DIFFRACTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/175148
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/175148
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditionsGaztañaga, Pablo ErnestoBaggio, Ricardo FortunatoVega, Daniel RobertoBENDAMUSTINE HYDROCHLORIDECRYSTAL STRUCTUREPOLYMORPHISMSINGLE-CRYSTAL X-RAY DIFFRACTIONhttps://purl.org/becyt/ford/1.3https://purl.org/becyt/ford/1Crystallographic, thermal and stability analyses are presented of three different anhydrated forms of bendamustine hydro­chloride [(I), (III) and (IV)] and a fourth, monohydrated one (II). Since form (I) presents the higher melting point and the higher heat of fusion, according to the 'heat of fusion' rule it should be the most stable in thermodynamic terms [Burger & Ramberger (1979). Mikrochim. Acta, 72, 259-271], though it is unstable in high-humidity conditions. The monohydrate structure (II), in turn, dehydrates by heating and topotactically transform into anhydrate (III). This latter form appears as less stable than anhydrate (I), to which it is linked via a monotropic relationship. For these three different forms, the crystal structure has been determined by single crystal X-ray diffraction. The crystal structures and molecular conformations of forms (II) and (III) are quite similar, as expected from the topotactic transformation linking them; furthermore, under high-humidity conditions, form (III) shows changes compatible with a transformation into form (II) within 24 h. The crystal structure of form (I) is different from the other two. The remaining polymorphic form (IV) could only be obtained as a powder, from which its crystalline structure could not be determined. The relative thermodynamic stability of the different crystalline forms was determined by differential scanning calorimetry and thermogravimetrical studies, and their stability under different humidity conditions analysed.Fil: Gaztañaga, Pablo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Baggio, Ricardo Fortunato. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Vega, Daniel Roberto. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaInternational Union of Crystallography2019-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/175148Gaztañaga, Pablo Ernesto; Baggio, Ricardo Fortunato; Vega, Daniel Roberto; Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions; International Union of Crystallography; Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials; 75; 10-2019; 933-9412052-5206CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://scripts.iucr.org/cgi-bin/paper?S2052520619010837info:eu-repo/semantics/altIdentifier/doi/10.1107/S2052520619010837info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:46:48Zoai:ri.conicet.gov.ar:11336/175148instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:46:48.905CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions
title Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions
spellingShingle Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions
Gaztañaga, Pablo Ernesto
BENDAMUSTINE HYDROCHLORIDE
CRYSTAL STRUCTURE
POLYMORPHISM
SINGLE-CRYSTAL X-RAY DIFFRACTION
title_short Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions
title_full Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions
title_fullStr Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions
title_full_unstemmed Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions
title_sort Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions
dc.creator.none.fl_str_mv Gaztañaga, Pablo Ernesto
Baggio, Ricardo Fortunato
Vega, Daniel Roberto
author Gaztañaga, Pablo Ernesto
author_facet Gaztañaga, Pablo Ernesto
Baggio, Ricardo Fortunato
Vega, Daniel Roberto
author_role author
author2 Baggio, Ricardo Fortunato
Vega, Daniel Roberto
author2_role author
author
dc.subject.none.fl_str_mv BENDAMUSTINE HYDROCHLORIDE
CRYSTAL STRUCTURE
POLYMORPHISM
SINGLE-CRYSTAL X-RAY DIFFRACTION
topic BENDAMUSTINE HYDROCHLORIDE
CRYSTAL STRUCTURE
POLYMORPHISM
SINGLE-CRYSTAL X-RAY DIFFRACTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Crystallographic, thermal and stability analyses are presented of three different anhydrated forms of bendamustine hydro­chloride [(I), (III) and (IV)] and a fourth, monohydrated one (II). Since form (I) presents the higher melting point and the higher heat of fusion, according to the 'heat of fusion' rule it should be the most stable in thermodynamic terms [Burger & Ramberger (1979). Mikrochim. Acta, 72, 259-271], though it is unstable in high-humidity conditions. The monohydrate structure (II), in turn, dehydrates by heating and topotactically transform into anhydrate (III). This latter form appears as less stable than anhydrate (I), to which it is linked via a monotropic relationship. For these three different forms, the crystal structure has been determined by single crystal X-ray diffraction. The crystal structures and molecular conformations of forms (II) and (III) are quite similar, as expected from the topotactic transformation linking them; furthermore, under high-humidity conditions, form (III) shows changes compatible with a transformation into form (II) within 24 h. The crystal structure of form (I) is different from the other two. The remaining polymorphic form (IV) could only be obtained as a powder, from which its crystalline structure could not be determined. The relative thermodynamic stability of the different crystalline forms was determined by differential scanning calorimetry and thermogravimetrical studies, and their stability under different humidity conditions analysed.
Fil: Gaztañaga, Pablo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Fil: Baggio, Ricardo Fortunato. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina
Fil: Vega, Daniel Roberto. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
description Crystallographic, thermal and stability analyses are presented of three different anhydrated forms of bendamustine hydro­chloride [(I), (III) and (IV)] and a fourth, monohydrated one (II). Since form (I) presents the higher melting point and the higher heat of fusion, according to the 'heat of fusion' rule it should be the most stable in thermodynamic terms [Burger & Ramberger (1979). Mikrochim. Acta, 72, 259-271], though it is unstable in high-humidity conditions. The monohydrate structure (II), in turn, dehydrates by heating and topotactically transform into anhydrate (III). This latter form appears as less stable than anhydrate (I), to which it is linked via a monotropic relationship. For these three different forms, the crystal structure has been determined by single crystal X-ray diffraction. The crystal structures and molecular conformations of forms (II) and (III) are quite similar, as expected from the topotactic transformation linking them; furthermore, under high-humidity conditions, form (III) shows changes compatible with a transformation into form (II) within 24 h. The crystal structure of form (I) is different from the other two. The remaining polymorphic form (IV) could only be obtained as a powder, from which its crystalline structure could not be determined. The relative thermodynamic stability of the different crystalline forms was determined by differential scanning calorimetry and thermogravimetrical studies, and their stability under different humidity conditions analysed.
publishDate 2019
dc.date.none.fl_str_mv 2019-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/175148
Gaztañaga, Pablo Ernesto; Baggio, Ricardo Fortunato; Vega, Daniel Roberto; Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions; International Union of Crystallography; Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials; 75; 10-2019; 933-941
2052-5206
CONICET Digital
CONICET
url http://hdl.handle.net/11336/175148
identifier_str_mv Gaztañaga, Pablo Ernesto; Baggio, Ricardo Fortunato; Vega, Daniel Roberto; Polymorphic forms of bendamustine hydro­chloride: crystal structure, thermal properties and stability at ambient conditions; International Union of Crystallography; Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials; 75; 10-2019; 933-941
2052-5206
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://scripts.iucr.org/cgi-bin/paper?S2052520619010837
info:eu-repo/semantics/altIdentifier/doi/10.1107/S2052520619010837
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv International Union of Crystallography
publisher.none.fl_str_mv International Union of Crystallography
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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