A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale

Autores
Catlin, Elise J.; Fandiño, Octavio Ezequiel; Lopez Vidal, Lucía; Sangalli, Martina; Donnelly, Ryan F.; Palma, Santiago Daniel; Paredes, Alejandro Javier
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Poor aqueous solubility of preexisting and emerging drug molecules is a common issue faced in the field of pharmaceutics. To address this, particle size reduction techniques, including drug micro- and nanonisation have been widely employed. Nanocrystals (NCs), drug particles with particle sizes below 1 µm, offer high drug content, improved dissolution, and long-acting capabilities. Media milling is the most used method to prepare NCs using of-the-shelf machinery, both at the laboratory and industrial scales. However, early NCs development, especially when limited amounts of the active are available, require the use of milligram-scale media milling. This study introduces a novel mini-scale milling device (Mini-mill) that incorporates temperature control through a water-cooled jacket. The device was used to produce NCs of three model hydrophobic drugs, itraconazole, ivermectin and curcumin, with lowest particle sizes of 162.5 ± 0.4 nm, 178 ± 2 nm, and 116.7 ± 0.7 nm, respectively. Precise control of milling temperature was achieved at 15, 45, and 75°C, with drug dependent particle size reduction trends, with no adverse effects on the milling materials or polymorphic changes in the NCs, as confirmed by calorimetric analysis. Finally, a scale-up feasibility study was carried out in a lab-scale NanoDisp®, confirming that the novel Mini-mills are a material-efficient tool for early formulation development, with potential for scale-up to commercial mills.
Fil: Catlin, Elise J.. The Queens University of Belfast; Irlanda
Fil: Fandiño, Octavio Ezequiel. The Queens University of Belfast; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lopez Vidal, Lucía. The Queens University of Belfast; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Sangalli, Martina. The Queens University of Belfast; Irlanda
Fil: Donnelly, Ryan F.. The Queens University of Belfast; Irlanda
Fil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Paredes, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. The Queens University of Belfast; Irlanda
Materia
Nanocrystals
Media milling
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:11336/262291
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scaleCatlin, Elise J.Fandiño, Octavio EzequielLopez Vidal, LucíaSangalli, MartinaDonnelly, Ryan F.Palma, Santiago DanielParedes, Alejandro JavierNanocrystalsMedia millinghttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2Poor aqueous solubility of preexisting and emerging drug molecules is a common issue faced in the field of pharmaceutics. To address this, particle size reduction techniques, including drug micro- and nanonisation have been widely employed. Nanocrystals (NCs), drug particles with particle sizes below 1 µm, offer high drug content, improved dissolution, and long-acting capabilities. Media milling is the most used method to prepare NCs using of-the-shelf machinery, both at the laboratory and industrial scales. However, early NCs development, especially when limited amounts of the active are available, require the use of milligram-scale media milling. This study introduces a novel mini-scale milling device (Mini-mill) that incorporates temperature control through a water-cooled jacket. The device was used to produce NCs of three model hydrophobic drugs, itraconazole, ivermectin and curcumin, with lowest particle sizes of 162.5 ± 0.4 nm, 178 ± 2 nm, and 116.7 ± 0.7 nm, respectively. Precise control of milling temperature was achieved at 15, 45, and 75°C, with drug dependent particle size reduction trends, with no adverse effects on the milling materials or polymorphic changes in the NCs, as confirmed by calorimetric analysis. Finally, a scale-up feasibility study was carried out in a lab-scale NanoDisp®, confirming that the novel Mini-mills are a material-efficient tool for early formulation development, with potential for scale-up to commercial mills.Fil: Catlin, Elise J.. The Queens University of Belfast; IrlandaFil: Fandiño, Octavio Ezequiel. The Queens University of Belfast; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lopez Vidal, Lucía. The Queens University of Belfast; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Sangalli, Martina. The Queens University of Belfast; IrlandaFil: Donnelly, Ryan F.. The Queens University of Belfast; IrlandaFil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Paredes, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. The Queens University of Belfast; IrlandaElsevier Science2024-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/262291Catlin, Elise J.; Fandiño, Octavio Ezequiel; Lopez Vidal, Lucía; Sangalli, Martina; Donnelly, Ryan F.; et al.; A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale; Elsevier Science; International Journal Of Pharmaceutics; 666; 12-2024; 1-130378-5173CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0378517324010147info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijpharm.2024.124780info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:23Zoai:ri.conicet.gov.ar:11336/262291instacron: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:34982025-09-03 09:59:24.188CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale
title A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale
spellingShingle A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale
Catlin, Elise J.
Nanocrystals
Media milling
title_short A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale
title_full A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale
title_fullStr A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale
title_full_unstemmed A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale
title_sort A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale
dc.creator.none.fl_str_mv Catlin, Elise J.
Fandiño, Octavio Ezequiel
Lopez Vidal, Lucía
Sangalli, Martina
Donnelly, Ryan F.
Palma, Santiago Daniel
Paredes, Alejandro Javier
author Catlin, Elise J.
author_facet Catlin, Elise J.
Fandiño, Octavio Ezequiel
Lopez Vidal, Lucía
Sangalli, Martina
Donnelly, Ryan F.
Palma, Santiago Daniel
Paredes, Alejandro Javier
author_role author
author2 Fandiño, Octavio Ezequiel
Lopez Vidal, Lucía
Sangalli, Martina
Donnelly, Ryan F.
Palma, Santiago Daniel
Paredes, Alejandro Javier
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Nanocrystals
Media milling
topic Nanocrystals
Media milling
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv Poor aqueous solubility of preexisting and emerging drug molecules is a common issue faced in the field of pharmaceutics. To address this, particle size reduction techniques, including drug micro- and nanonisation have been widely employed. Nanocrystals (NCs), drug particles with particle sizes below 1 µm, offer high drug content, improved dissolution, and long-acting capabilities. Media milling is the most used method to prepare NCs using of-the-shelf machinery, both at the laboratory and industrial scales. However, early NCs development, especially when limited amounts of the active are available, require the use of milligram-scale media milling. This study introduces a novel mini-scale milling device (Mini-mill) that incorporates temperature control through a water-cooled jacket. The device was used to produce NCs of three model hydrophobic drugs, itraconazole, ivermectin and curcumin, with lowest particle sizes of 162.5 ± 0.4 nm, 178 ± 2 nm, and 116.7 ± 0.7 nm, respectively. Precise control of milling temperature was achieved at 15, 45, and 75°C, with drug dependent particle size reduction trends, with no adverse effects on the milling materials or polymorphic changes in the NCs, as confirmed by calorimetric analysis. Finally, a scale-up feasibility study was carried out in a lab-scale NanoDisp®, confirming that the novel Mini-mills are a material-efficient tool for early formulation development, with potential for scale-up to commercial mills.
Fil: Catlin, Elise J.. The Queens University of Belfast; Irlanda
Fil: Fandiño, Octavio Ezequiel. The Queens University of Belfast; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lopez Vidal, Lucía. The Queens University of Belfast; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Sangalli, Martina. The Queens University of Belfast; Irlanda
Fil: Donnelly, Ryan F.. The Queens University of Belfast; Irlanda
Fil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Paredes, Alejandro Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. The Queens University of Belfast; Irlanda
description Poor aqueous solubility of preexisting and emerging drug molecules is a common issue faced in the field of pharmaceutics. To address this, particle size reduction techniques, including drug micro- and nanonisation have been widely employed. Nanocrystals (NCs), drug particles with particle sizes below 1 µm, offer high drug content, improved dissolution, and long-acting capabilities. Media milling is the most used method to prepare NCs using of-the-shelf machinery, both at the laboratory and industrial scales. However, early NCs development, especially when limited amounts of the active are available, require the use of milligram-scale media milling. This study introduces a novel mini-scale milling device (Mini-mill) that incorporates temperature control through a water-cooled jacket. The device was used to produce NCs of three model hydrophobic drugs, itraconazole, ivermectin and curcumin, with lowest particle sizes of 162.5 ± 0.4 nm, 178 ± 2 nm, and 116.7 ± 0.7 nm, respectively. Precise control of milling temperature was achieved at 15, 45, and 75°C, with drug dependent particle size reduction trends, with no adverse effects on the milling materials or polymorphic changes in the NCs, as confirmed by calorimetric analysis. Finally, a scale-up feasibility study was carried out in a lab-scale NanoDisp®, confirming that the novel Mini-mills are a material-efficient tool for early formulation development, with potential for scale-up to commercial mills.
publishDate 2024
dc.date.none.fl_str_mv 2024-12
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/11336/262291
Catlin, Elise J.; Fandiño, Octavio Ezequiel; Lopez Vidal, Lucía; Sangalli, Martina; Donnelly, Ryan F.; et al.; A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale; Elsevier Science; International Journal Of Pharmaceutics; 666; 12-2024; 1-13
0378-5173
CONICET Digital
CONICET
url http://hdl.handle.net/11336/262291
identifier_str_mv Catlin, Elise J.; Fandiño, Octavio Ezequiel; Lopez Vidal, Lucía; Sangalli, Martina; Donnelly, Ryan F.; et al.; A novel temperature-controlled media milling device to produce drug nanocrystals at the laboratory scale; Elsevier Science; International Journal Of Pharmaceutics; 666; 12-2024; 1-13
0378-5173
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0378517324010147
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijpharm.2024.124780
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 Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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 13.13397

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