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Interfacial stress and container failure during freezing of bulk protein solutions can be prevented by local heating

2020-10Journal article Open access
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dc.contributor.authorDuarte, Andreia
dc.contributor.authorRego, Pedro
dc.contributor.authorFerreira, Aida
dc.contributor.authorDias, Paulo
dc.contributor.authorGeraldes, Vítor
dc.contributor.authorRodrigues, Miguel A.
dc.date.accessioned2020-09-14T15:01:13Z
dc.date.available2020-09-14T15:01:13Z
dc.date.issued2020-10
dc.descriptionLisboa 2020_Project 17653_Cryocubept_PT
dc.description.abstractBottles and carboys are used for frozen storage and transport of biopharmaceutical formulations under a wide range of conditions. The quality of freezing and thawing in these systems has been questioned due to the formation of heterogeneous ice structures and the deformation of containers. This work shows that during freezing of bulk protein solutions, the liquid at the air-liquid interface freezes first, forming an ice crust and enclosing the liquid phase. As the enclosed liquid freezes, internal pressure rises, pushing the liquid phase through the porous ice crust towards the air interface, leading to interfacial stress and protein aggregation. The aggregation of bovine serum albumin was more intense in the foam-like ice mound that was formed at the top, where bubbles were entrapped. This was characterized experimentally with the assistance of magnetic resonance imaging (MRI). An isothermal cover is proposed to prevent the early freezing of the liquid at the air interface, attenuating substantially interfacial stress to proteins and releasing hydrostatic pressure, preserving the shape and integrity of the containers.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationDuarte A, Rego P, Ferreira A, Dias P, Geraldes V, Rodrigues MA. Interfacial stress and container failure during freezing of bulk protein solutions can be prevented by local heating. AAPS PharmSciTech. 2020;21(7):ID251.pt_PT
dc.identifier.doi10.1208/s12249-020-01794-xpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/12232
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringerpt_PT
dc.relationLisboa 2020_Project 17653_Cryocubept_PT
dc.relation.publisherversionhttps://link.springer.com/article/10.1208%2Fs12249-020-01794-xpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectFreezingpt_PT
dc.subjectIce crustpt_PT
dc.subjectInterfacial stresspt_PT
dc.subjectIsothermal coverpt_PT
dc.subjectPressure increasept_PT
dc.titleInterfacial stress and container failure during freezing of bulk protein solutions can be prevented by local heatingpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue7pt_PT
oaire.citation.startPage251pt_PT
oaire.citation.titleAAPS PharmSciTechpt_PT
oaire.citation.volume21pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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