Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms

Although not readily accessible yet to many community and hospital pharmacists, fuse deposition modelling (FDM) is a 3D printing technique that can be used to create a 3D pharmaceutical dosage form by employing drug loaded filaments extruded via a nozzle, melted and deposited layer by layer. FDM req...

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Autores: Cerda, Jose R., Arifi, Talaya, Ayyoubi, Sejad, Knief, Peter, Ballesteros Papantonakis, María De La Paloma, Keeble, William, Barbu, Eugen, Healy, Anne Marie, Lalatsa, Aikaterini, Serrano López, Dolores Remedios
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/6778
Acceso en línea:https://hdl.handle.net/20.500.14352/6778
Access Level:acceso abierto
Palabra clave:615.01/.03
3D printing
Fused deposition modelling (FDM)
Hansen Solubility Parameters
passive diffusion
Filaments
PVA
PLA
Nifedipine
Farmacología (Farmacia)
3209 Farmacología
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network_acronym_str ES
network_name_str España
repository_id_str
spelling Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage FormsCerda, Jose R.Arifi, TalayaAyyoubi, SejadKnief, PeterBallesteros Papantonakis, María De La PalomaKeeble, WilliamBarbu, EugenHealy, Anne MarieLalatsa, AikateriniSerrano López, Dolores Remedios615.01/.033D printingFused deposition modelling (FDM)Hansen Solubility Parameterspassive diffusionFilamentsPVAPLANifedipineFarmacología (Farmacia)3209 FarmacologíaAlthough not readily accessible yet to many community and hospital pharmacists, fuse deposition modelling (FDM) is a 3D printing technique that can be used to create a 3D pharmaceutical dosage form by employing drug loaded filaments extruded via a nozzle, melted and deposited layer by layer. FDM requires printable filaments, which are commonly manufactured by hot melt extrusion, and identifying a suitable extrudable drug-excipient mixture can sometimes be challenging. We propose here the use of passive diffusion as an accessible loading method for filaments that can be printed using FDM technology to allow for the fabrication of oral personalised medicines in clinical settings. Utilising Hansen Solubility Parameters (HSP) and the concept of HSP distances (Ra) between drug, solvent, and filament, we have developed a facile pre-screening tool for the selection of the optimal combination that can provide a high drug loading (a high solvent-drug Ra, >10, and an intermediate solvent filament Ra value, ~10). We have identified that other parameters such as surface roughness and stiffness also play a key role in enhancing passive diffusion of the drug into the filaments. A predictive model for drug loading was developed based on Support Vector Machine (SVM) regression and indicated a strong correlation between both Ra and filament stiffness and the diffusion capacity of a model BCS Class II drug, nifedipine (NFD), into the filaments. A drug loading, close to 3% w/w, was achieved. 3D printed tablets prepared using a PVA-derived filament (Hydrosupport, 3D Fuel) showed promising characteristics in terms of dissolution (with a sustained release over 24 h) and predicted chemical stability (>3 years at 25 ◦C/60% relative humidity), similar to commercially available NFD oral dosage forms. We believe FDM coupled with passive diffusion could be implemented easily in clinical settings for the manufacture of tailored personalised medicines, which can be stored over long periods of time (similar to industrially manufactured solid dosage forms).MDPIUniversidad Complutense de Madrid20202020-04-1120202020-04-11journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/6778reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/67782026-06-02T12:44:21Z
dc.title.none.fl_str_mv Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms
title Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms
spellingShingle Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms
Cerda, Jose R.
615.01/.03
3D printing
Fused deposition modelling (FDM)
Hansen Solubility Parameters
passive diffusion
Filaments
PVA
PLA
Nifedipine
Farmacología (Farmacia)
3209 Farmacología
title_short Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms
title_full Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms
title_fullStr Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms
title_full_unstemmed Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms
title_sort Personalised 3D Printed Medicines: Optimising Material Properties for Successful Passive Diffusion Loading of Filaments for Fused Deposition Modelling of Solid Dosage Forms
dc.creator.none.fl_str_mv Cerda, Jose R.
Arifi, Talaya
Ayyoubi, Sejad
Knief, Peter
Ballesteros Papantonakis, María De La Paloma
Keeble, William
Barbu, Eugen
Healy, Anne Marie
Lalatsa, Aikaterini
Serrano López, Dolores Remedios
author Cerda, Jose R.
author_facet Cerda, Jose R.
Arifi, Talaya
Ayyoubi, Sejad
Knief, Peter
Ballesteros Papantonakis, María De La Paloma
Keeble, William
Barbu, Eugen
Healy, Anne Marie
Lalatsa, Aikaterini
Serrano López, Dolores Remedios
author_role author
author2 Arifi, Talaya
Ayyoubi, Sejad
Knief, Peter
Ballesteros Papantonakis, María De La Paloma
Keeble, William
Barbu, Eugen
Healy, Anne Marie
Lalatsa, Aikaterini
Serrano López, Dolores Remedios
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 615.01/.03
3D printing
Fused deposition modelling (FDM)
Hansen Solubility Parameters
passive diffusion
Filaments
PVA
PLA
Nifedipine
Farmacología (Farmacia)
3209 Farmacología
topic 615.01/.03
3D printing
Fused deposition modelling (FDM)
Hansen Solubility Parameters
passive diffusion
Filaments
PVA
PLA
Nifedipine
Farmacología (Farmacia)
3209 Farmacología
description Although not readily accessible yet to many community and hospital pharmacists, fuse deposition modelling (FDM) is a 3D printing technique that can be used to create a 3D pharmaceutical dosage form by employing drug loaded filaments extruded via a nozzle, melted and deposited layer by layer. FDM requires printable filaments, which are commonly manufactured by hot melt extrusion, and identifying a suitable extrudable drug-excipient mixture can sometimes be challenging. We propose here the use of passive diffusion as an accessible loading method for filaments that can be printed using FDM technology to allow for the fabrication of oral personalised medicines in clinical settings. Utilising Hansen Solubility Parameters (HSP) and the concept of HSP distances (Ra) between drug, solvent, and filament, we have developed a facile pre-screening tool for the selection of the optimal combination that can provide a high drug loading (a high solvent-drug Ra, >10, and an intermediate solvent filament Ra value, ~10). We have identified that other parameters such as surface roughness and stiffness also play a key role in enhancing passive diffusion of the drug into the filaments. A predictive model for drug loading was developed based on Support Vector Machine (SVM) regression and indicated a strong correlation between both Ra and filament stiffness and the diffusion capacity of a model BCS Class II drug, nifedipine (NFD), into the filaments. A drug loading, close to 3% w/w, was achieved. 3D printed tablets prepared using a PVA-derived filament (Hydrosupport, 3D Fuel) showed promising characteristics in terms of dissolution (with a sustained release over 24 h) and predicted chemical stability (>3 years at 25 ◦C/60% relative humidity), similar to commercially available NFD oral dosage forms. We believe FDM coupled with passive diffusion could be implemented easily in clinical settings for the manufacture of tailored personalised medicines, which can be stored over long periods of time (similar to industrially manufactured solid dosage forms).
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-04-11
2020
2020-04-11
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/6778
url https://hdl.handle.net/20.500.14352/6778
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
Atribución 3.0 España
https://creativecommons.org/licenses/by/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
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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