Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comilling

Amorphous dispersions of the Biclotymol antiseptic are obtained in polyvinylpyrrolidone (PVP), for different drug loadings, by comilling at temperatures below the glass transition of both components. Characterization of the dispersions by scanning differential calorimetry and temperature-dependent b...

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Autores: Romanini, Michela|||0000-0002-1685-855X, Lorente, Marta, Schammé, Benjamin, Delbreilh, Laurent, Dupray, Valérie, Coquerel, Gerard, Tamarit Mur, José Luis|||0000-0002-7965-0000, Macovez, Roberto|||0000-0001-5026-9372
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/129503
Acceso en línea:https://hdl.handle.net/2117/129503
https://dx.doi.org/10.1021/acs.macromol.8b01271
Access Level:acceso abierto
Palabra clave:Chemical engineering
Enginyeria química
Àrees temàtiques de la UPC::Enginyeria química
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spelling Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comillingRomanini, Michela|||0000-0002-1685-855XLorente, MartaSchammé, BenjaminDelbreilh, LaurentDupray, ValérieCoquerel, GerardTamarit Mur, José Luis|||0000-0002-7965-0000Macovez, Roberto|||0000-0001-5026-9372Chemical engineeringEnginyeria químicaÀrees temàtiques de la UPC::Enginyeria químicaAmorphous dispersions of the Biclotymol antiseptic are obtained in polyvinylpyrrolidone (PVP), for different drug loadings, by comilling at temperatures below the glass transition of both components. Characterization of the dispersions by scanning differential calorimetry and temperature-dependent broadband dielectric spectroscopy shows them to be homogeneous amorphous molecular mixtures. A single glass transition with pronounced enthalpy recovery peak is observed, indicative of the formation of a homogeneous glass state characterized by substantial aging. The polymer has a considerable antiplasticizing effect on the drug, increasing its glass transition temperature (Tg) to well above room temperature. The Tg of the mixture increases linearly with the macromolecular mass fraction. Three (macro)molecular relaxations are identified in the isothermal dielectric spectra of the mixtures. The slowest process corresponds to the cooperative (a relaxation) dynamics of the polymer chains and drug molecules simultaneously, and its relaxation time becomes longer the higher the polymer content. The fastest one is an intramolecular relaxation mode of Biclotymol and is virtually unaffected by the presence of the polymer. Finally, the intermediate relaxation, which is also observed in pure PVP, is assigned to the motion of the polymer side groups. Its activation barrier increases with increasing drug content, indicative of a direct interaction of the drug with the pyrrolidone moieties, likely via hydrogen bonding to the carbonyl oxygen. Contrary to pure PVP, the mixtures are not hygroscopic. Mechanical amorphization by cryomilling thus yields glassy molecular mixtures at arbitrary drug concentration, with enhanced physical stability against crystallization and enhanced chemical stability against hydrolysis reactions.Peer ReviewedAmerican Chemical Society (ACS)20182018-11-2720192019-02-21journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/129503https://dx.doi.org/10.1021/acs.macromol.8b01271reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivs 3.0 Spainhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/1295032026-05-27T15:37:01Z
dc.title.none.fl_str_mv Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comilling
title Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comilling
spellingShingle Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comilling
Romanini, Michela|||0000-0002-1685-855X
Chemical engineering
Enginyeria química
Àrees temàtiques de la UPC::Enginyeria química
title_short Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comilling
title_full Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comilling
title_fullStr Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comilling
title_full_unstemmed Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comilling
title_sort Enhancement of the physical and chemical stability of amorphous drug-polymer mixtures via cryogenic comilling
dc.creator.none.fl_str_mv Romanini, Michela|||0000-0002-1685-855X
Lorente, Marta
Schammé, Benjamin
Delbreilh, Laurent
Dupray, Valérie
Coquerel, Gerard
Tamarit Mur, José Luis|||0000-0002-7965-0000
Macovez, Roberto|||0000-0001-5026-9372
author Romanini, Michela|||0000-0002-1685-855X
author_facet Romanini, Michela|||0000-0002-1685-855X
Lorente, Marta
Schammé, Benjamin
Delbreilh, Laurent
Dupray, Valérie
Coquerel, Gerard
Tamarit Mur, José Luis|||0000-0002-7965-0000
Macovez, Roberto|||0000-0001-5026-9372
author_role author
author2 Lorente, Marta
Schammé, Benjamin
Delbreilh, Laurent
Dupray, Valérie
Coquerel, Gerard
Tamarit Mur, José Luis|||0000-0002-7965-0000
Macovez, Roberto|||0000-0001-5026-9372
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Chemical engineering
Enginyeria química
Àrees temàtiques de la UPC::Enginyeria química
topic Chemical engineering
Enginyeria química
Àrees temàtiques de la UPC::Enginyeria química
description Amorphous dispersions of the Biclotymol antiseptic are obtained in polyvinylpyrrolidone (PVP), for different drug loadings, by comilling at temperatures below the glass transition of both components. Characterization of the dispersions by scanning differential calorimetry and temperature-dependent broadband dielectric spectroscopy shows them to be homogeneous amorphous molecular mixtures. A single glass transition with pronounced enthalpy recovery peak is observed, indicative of the formation of a homogeneous glass state characterized by substantial aging. The polymer has a considerable antiplasticizing effect on the drug, increasing its glass transition temperature (Tg) to well above room temperature. The Tg of the mixture increases linearly with the macromolecular mass fraction. Three (macro)molecular relaxations are identified in the isothermal dielectric spectra of the mixtures. The slowest process corresponds to the cooperative (a relaxation) dynamics of the polymer chains and drug molecules simultaneously, and its relaxation time becomes longer the higher the polymer content. The fastest one is an intramolecular relaxation mode of Biclotymol and is virtually unaffected by the presence of the polymer. Finally, the intermediate relaxation, which is also observed in pure PVP, is assigned to the motion of the polymer side groups. Its activation barrier increases with increasing drug content, indicative of a direct interaction of the drug with the pyrrolidone moieties, likely via hydrogen bonding to the carbonyl oxygen. Contrary to pure PVP, the mixtures are not hygroscopic. Mechanical amorphization by cryomilling thus yields glassy molecular mixtures at arbitrary drug concentration, with enhanced physical stability against crystallization and enhanced chemical stability against hydrolysis reactions.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-11-27
2019
2019-02-21
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/129503
https://dx.doi.org/10.1021/acs.macromol.8b01271
url https://hdl.handle.net/2117/129503
https://dx.doi.org/10.1021/acs.macromol.8b01271
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Chemical Society (ACS)
publisher.none.fl_str_mv American Chemical Society (ACS)
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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