Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing

Biotinidase deficiency is a rare inherited disorder characterized by biotin metabolism issues, leading to neurological and cutaneous symptoms that can be alleviated through biotin administration. Three-dimensional (3D) printing (3DP) offers potential for personalized medicine production for rare dis...

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Autores: Mora Castaño, Gloria, Rodríguez Pombo, Lucía, Carou-Senra, Paola, Januskaite, Patricija, Rial, Carlos, Bendicho-Lavilla, Carlos, Couce, Maria L., Millán Jiménez, Mónica, Caraballo Rodríguez, Isidoro, Basit, Abdul W., Alvarez-Lorenzo, Carmen, Goyanes, Alvaro
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/172003
Acesso em linha:https://hdl.handle.net/11441/172003
https://doi.org/10.1016/j.ijpharm.2024.124964
Access Level:acceso abierto
Palavra-chave:3D printed pharmaceuticals
Additive manufacturing
Drug delivery systems
Modified release formulations
Rare metabolic disorders
Pediatric precision treatments
Pharma-inks
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spelling Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printingMora Castaño, GloriaRodríguez Pombo, LucíaCarou-Senra, PaolaJanuskaite, PatricijaRial, CarlosBendicho-Lavilla, CarlosCouce, Maria L.Millán Jiménez, MónicaCaraballo Rodríguez, IsidoroBasit, Abdul W.Alvarez-Lorenzo, CarmenGoyanes, Alvaro3D printed pharmaceuticalsAdditive manufacturingDrug delivery systemsModified release formulationsRare metabolic disordersPediatric precision treatmentsPharma-inksBiotinidase deficiency is a rare inherited disorder characterized by biotin metabolism issues, leading to neurological and cutaneous symptoms that can be alleviated through biotin administration. Three-dimensional (3D) printing (3DP) offers potential for personalized medicine production for rare diseases, due to its flexibility in designing dosage forms and controlling release profiles. For such point-of-care applications, rigorous quality control (QC) measures are essential to ensure precise dosing, optimal performance, and product safety, especially for low personalized doses in preclinical and clinical studies. In this work, we addressed QC challenges by integrating a precision balance into a direct powder extrusion pharmaceutical 3D printer (M3DIMAKER™) for real-time, in-line mass uniformity testing, a critical quality control step. Small and large capsule-shaped biotin printlets (3D printed tablets) for immediate- and extended-release were printed. The integrated balance monitored and registered each printlet’s weight, identifying any deviations from acceptable limits. While all large printlet batches met mass uniformity criteria, some small printlet batches exhibited weight deviations. In vitro release studies showed large immediate-release printlets releasing 82% of biotin within 45 min, compared to 100% for small immediate-release printlets. For extended-release formulations, 35% of the drug was released from small printlets, whereas 24% was released from large printlets at the same time point. The integration of process analytical technology tools in 3DP shows promise in enhancing QC and scalability of personalized dosing at the point-of-care, demonstrating successful integration of a balance into a direct powder extrusion 3D printer for in-line mass uniformity testing across different sizes of capsule-shaped printlets.ElsevierFarmacia y Tecnología FarmacéuticaMinisterio de Ciencia, Innovación y Universidades (MICIU). EspañaXunta de GaliciaFundación Mutua MadrileñaEngineering and Physical Sciences Research Council (EPSRC)2025info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/172003https://doi.org/10.1016/j.ijpharm.2024.124964reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésInternational Journal of Pharmaceutics, 668, 124964.ED481A 2023AP180872022EP/S023054/1PID2023-149544OB-C22https://doi.org/10.1016/j.ijpharm.2024.124964info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1720032026-06-17T12:51:07Z
dc.title.none.fl_str_mv Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
title Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
spellingShingle Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
Mora Castaño, Gloria
3D printed pharmaceuticals
Additive manufacturing
Drug delivery systems
Modified release formulations
Rare metabolic disorders
Pediatric precision treatments
Pharma-inks
title_short Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
title_full Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
title_fullStr Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
title_full_unstemmed Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
title_sort Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
dc.creator.none.fl_str_mv Mora Castaño, Gloria
Rodríguez Pombo, Lucía
Carou-Senra, Paola
Januskaite, Patricija
Rial, Carlos
Bendicho-Lavilla, Carlos
Couce, Maria L.
Millán Jiménez, Mónica
Caraballo Rodríguez, Isidoro
Basit, Abdul W.
Alvarez-Lorenzo, Carmen
Goyanes, Alvaro
author Mora Castaño, Gloria
author_facet Mora Castaño, Gloria
Rodríguez Pombo, Lucía
Carou-Senra, Paola
Januskaite, Patricija
Rial, Carlos
Bendicho-Lavilla, Carlos
Couce, Maria L.
Millán Jiménez, Mónica
Caraballo Rodríguez, Isidoro
Basit, Abdul W.
Alvarez-Lorenzo, Carmen
Goyanes, Alvaro
author_role author
author2 Rodríguez Pombo, Lucía
Carou-Senra, Paola
Januskaite, Patricija
Rial, Carlos
Bendicho-Lavilla, Carlos
Couce, Maria L.
Millán Jiménez, Mónica
Caraballo Rodríguez, Isidoro
Basit, Abdul W.
Alvarez-Lorenzo, Carmen
Goyanes, Alvaro
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Farmacia y Tecnología Farmacéutica
Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Xunta de Galicia
Fundación Mutua Madrileña
Engineering and Physical Sciences Research Council (EPSRC)
dc.subject.none.fl_str_mv 3D printed pharmaceuticals
Additive manufacturing
Drug delivery systems
Modified release formulations
Rare metabolic disorders
Pediatric precision treatments
Pharma-inks
topic 3D printed pharmaceuticals
Additive manufacturing
Drug delivery systems
Modified release formulations
Rare metabolic disorders
Pediatric precision treatments
Pharma-inks
description Biotinidase deficiency is a rare inherited disorder characterized by biotin metabolism issues, leading to neurological and cutaneous symptoms that can be alleviated through biotin administration. Three-dimensional (3D) printing (3DP) offers potential for personalized medicine production for rare diseases, due to its flexibility in designing dosage forms and controlling release profiles. For such point-of-care applications, rigorous quality control (QC) measures are essential to ensure precise dosing, optimal performance, and product safety, especially for low personalized doses in preclinical and clinical studies. In this work, we addressed QC challenges by integrating a precision balance into a direct powder extrusion pharmaceutical 3D printer (M3DIMAKER™) for real-time, in-line mass uniformity testing, a critical quality control step. Small and large capsule-shaped biotin printlets (3D printed tablets) for immediate- and extended-release were printed. The integrated balance monitored and registered each printlet’s weight, identifying any deviations from acceptable limits. While all large printlet batches met mass uniformity criteria, some small printlet batches exhibited weight deviations. In vitro release studies showed large immediate-release printlets releasing 82% of biotin within 45 min, compared to 100% for small immediate-release printlets. For extended-release formulations, 35% of the drug was released from small printlets, whereas 24% was released from large printlets at the same time point. The integration of process analytical technology tools in 3DP shows promise in enhancing QC and scalability of personalized dosing at the point-of-care, demonstrating successful integration of a balance into a direct powder extrusion 3D printer for in-line mass uniformity testing across different sizes of capsule-shaped printlets.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/172003
https://doi.org/10.1016/j.ijpharm.2024.124964
url https://hdl.handle.net/11441/172003
https://doi.org/10.1016/j.ijpharm.2024.124964
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv International Journal of Pharmaceutics, 668, 124964.
ED481A 2023
AP180872022
EP/S023054/1
PID2023-149544OB-C22
https://doi.org/10.1016/j.ijpharm.2024.124964
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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