Preparation and characterization of polymorphs of the glucocorticoid deflazacort

Autores
Kassuha, Diego Enrique; Aiassa, Virginia; Bruno, Flavia Paola; Cuadra, Gabriel R.; Sperandeo, Norma Rebeca
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The polymorphism of new and old active pharmaceutical ingredients (APIs) is of great importance due to performance, stability and processability aspects. The objective of this study was to investigate the polymorphism of deflazacort (DEF), a glucocorticoid discovered >40 years ago, since this phenomenon has not been previously investigated for this API. Using different methods for solid form screening, it was determined for the first time that DEF is able to exist as three forms: a crystalline (DEF-1); a hydrated X-ray amorphous (DEF-t-bw) and an anhydrous amorphous phase (DEF-g) obtained from manually grinding DEF-1. The in vitro and in vivo dissolution rates (DRs) of DEF-1 and DEF-t-bw, which were measured using the rotating disk method in water at 37 °C and the pellet implantation technique in rats, respectively, indicated that DEF-t-bw exhibited slightly faster in vitro and in vivo DRs than those of the crystalline form, but the values were not significantly different. In addition, it was determined that DEF-t-bw devitrifies to DEF-1 by the effect of pressure, humidity and heat. It was concluded that DEF is glucorticoid with low tendency to exhibit different crystalline forms and that DEF-t-bw has no advantages over DEF-1 in terms of solubility, DRs and solid-state stability.
Fil: Kassuha, Diego Enrique. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aiassa, Virginia. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bruno, Flavia Paola. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cuadra, Gabriel R.. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sperandeo, Norma Rebeca. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Crystallization
Deflazacort
Disk Intrinsic/In Vivo Dissolution Rates
Polymorphism
Powder X-Ray Diffractometry
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25277
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/25277
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network_name_str CONICET Digital (CONICET)
spelling Preparation and characterization of polymorphs of the glucocorticoid deflazacortKassuha, Diego EnriqueAiassa, VirginiaBruno, Flavia PaolaCuadra, Gabriel R.Sperandeo, Norma RebecaCrystallizationDeflazacortDisk Intrinsic/In Vivo Dissolution RatesPolymorphismPowder X-Ray Diffractometryhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The polymorphism of new and old active pharmaceutical ingredients (APIs) is of great importance due to performance, stability and processability aspects. The objective of this study was to investigate the polymorphism of deflazacort (DEF), a glucocorticoid discovered >40 years ago, since this phenomenon has not been previously investigated for this API. Using different methods for solid form screening, it was determined for the first time that DEF is able to exist as three forms: a crystalline (DEF-1); a hydrated X-ray amorphous (DEF-t-bw) and an anhydrous amorphous phase (DEF-g) obtained from manually grinding DEF-1. The in vitro and in vivo dissolution rates (DRs) of DEF-1 and DEF-t-bw, which were measured using the rotating disk method in water at 37 °C and the pellet implantation technique in rats, respectively, indicated that DEF-t-bw exhibited slightly faster in vitro and in vivo DRs than those of the crystalline form, but the values were not significantly different. In addition, it was determined that DEF-t-bw devitrifies to DEF-1 by the effect of pressure, humidity and heat. It was concluded that DEF is glucorticoid with low tendency to exhibit different crystalline forms and that DEF-t-bw has no advantages over DEF-1 in terms of solubility, DRs and solid-state stability.Fil: Kassuha, Diego Enrique. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aiassa, Virginia. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bruno, Flavia Paola. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cuadra, Gabriel R.. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sperandeo, Norma Rebeca. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaTaylor & Francis2014-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25277Kassuha, Diego Enrique; Aiassa, Virginia; Bruno, Flavia Paola; Cuadra, Gabriel R.; Sperandeo, Norma Rebeca; Preparation and characterization of polymorphs of the glucocorticoid deflazacort; Taylor & Francis; Pharmaceutical Development and Technology; 20; 4; 1-2014; 401-4091083-7450CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3109/10837450.2013.871033info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/10837450.2013.871033info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:13:38Zoai:ri.conicet.gov.ar:11336/25277instacron: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:34982025-09-10 13:13:38.418CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Preparation and characterization of polymorphs of the glucocorticoid deflazacort
title Preparation and characterization of polymorphs of the glucocorticoid deflazacort
spellingShingle Preparation and characterization of polymorphs of the glucocorticoid deflazacort
Kassuha, Diego Enrique
Crystallization
Deflazacort
Disk Intrinsic/In Vivo Dissolution Rates
Polymorphism
Powder X-Ray Diffractometry
title_short Preparation and characterization of polymorphs of the glucocorticoid deflazacort
title_full Preparation and characterization of polymorphs of the glucocorticoid deflazacort
title_fullStr Preparation and characterization of polymorphs of the glucocorticoid deflazacort
title_full_unstemmed Preparation and characterization of polymorphs of the glucocorticoid deflazacort
title_sort Preparation and characterization of polymorphs of the glucocorticoid deflazacort
dc.creator.none.fl_str_mv Kassuha, Diego Enrique
Aiassa, Virginia
Bruno, Flavia Paola
Cuadra, Gabriel R.
Sperandeo, Norma Rebeca
author Kassuha, Diego Enrique
author_facet Kassuha, Diego Enrique
Aiassa, Virginia
Bruno, Flavia Paola
Cuadra, Gabriel R.
Sperandeo, Norma Rebeca
author_role author
author2 Aiassa, Virginia
Bruno, Flavia Paola
Cuadra, Gabriel R.
Sperandeo, Norma Rebeca
author2_role author
author
author
author
dc.subject.none.fl_str_mv Crystallization
Deflazacort
Disk Intrinsic/In Vivo Dissolution Rates
Polymorphism
Powder X-Ray Diffractometry
topic Crystallization
Deflazacort
Disk Intrinsic/In Vivo Dissolution Rates
Polymorphism
Powder X-Ray Diffractometry
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The polymorphism of new and old active pharmaceutical ingredients (APIs) is of great importance due to performance, stability and processability aspects. The objective of this study was to investigate the polymorphism of deflazacort (DEF), a glucocorticoid discovered >40 years ago, since this phenomenon has not been previously investigated for this API. Using different methods for solid form screening, it was determined for the first time that DEF is able to exist as three forms: a crystalline (DEF-1); a hydrated X-ray amorphous (DEF-t-bw) and an anhydrous amorphous phase (DEF-g) obtained from manually grinding DEF-1. The in vitro and in vivo dissolution rates (DRs) of DEF-1 and DEF-t-bw, which were measured using the rotating disk method in water at 37 °C and the pellet implantation technique in rats, respectively, indicated that DEF-t-bw exhibited slightly faster in vitro and in vivo DRs than those of the crystalline form, but the values were not significantly different. In addition, it was determined that DEF-t-bw devitrifies to DEF-1 by the effect of pressure, humidity and heat. It was concluded that DEF is glucorticoid with low tendency to exhibit different crystalline forms and that DEF-t-bw has no advantages over DEF-1 in terms of solubility, DRs and solid-state stability.
Fil: Kassuha, Diego Enrique. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aiassa, Virginia. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bruno, Flavia Paola. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cuadra, Gabriel R.. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sperandeo, Norma Rebeca. Universidad Nacional de Cordoba. Facultad de Ciencias Quimicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The polymorphism of new and old active pharmaceutical ingredients (APIs) is of great importance due to performance, stability and processability aspects. The objective of this study was to investigate the polymorphism of deflazacort (DEF), a glucocorticoid discovered >40 years ago, since this phenomenon has not been previously investigated for this API. Using different methods for solid form screening, it was determined for the first time that DEF is able to exist as three forms: a crystalline (DEF-1); a hydrated X-ray amorphous (DEF-t-bw) and an anhydrous amorphous phase (DEF-g) obtained from manually grinding DEF-1. The in vitro and in vivo dissolution rates (DRs) of DEF-1 and DEF-t-bw, which were measured using the rotating disk method in water at 37 °C and the pellet implantation technique in rats, respectively, indicated that DEF-t-bw exhibited slightly faster in vitro and in vivo DRs than those of the crystalline form, but the values were not significantly different. In addition, it was determined that DEF-t-bw devitrifies to DEF-1 by the effect of pressure, humidity and heat. It was concluded that DEF is glucorticoid with low tendency to exhibit different crystalline forms and that DEF-t-bw has no advantages over DEF-1 in terms of solubility, DRs and solid-state stability.
publishDate 2014
dc.date.none.fl_str_mv 2014-01
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/11336/25277
Kassuha, Diego Enrique; Aiassa, Virginia; Bruno, Flavia Paola; Cuadra, Gabriel R.; Sperandeo, Norma Rebeca; Preparation and characterization of polymorphs of the glucocorticoid deflazacort; Taylor & Francis; Pharmaceutical Development and Technology; 20; 4; 1-2014; 401-409
1083-7450
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25277
identifier_str_mv Kassuha, Diego Enrique; Aiassa, Virginia; Bruno, Flavia Paola; Cuadra, Gabriel R.; Sperandeo, Norma Rebeca; Preparation and characterization of polymorphs of the glucocorticoid deflazacort; Taylor & Francis; Pharmaceutical Development and Technology; 20; 4; 1-2014; 401-409
1083-7450
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3109/10837450.2013.871033
info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/10837450.2013.871033
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
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 12.993085

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