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Development of Composite, Reinforced, Highly Drug-Loaded Pharmaceutical Printlets Manufactured by Selective Laser Sintering—In Search of Relevant Excipients for Pharmaceutical 3D Printing
3D printing by selective laser sintering (SLS) of high-dose drug delivery systems using pure brittle crystalline active pharmaceutical ingredients (API) is possible but impractical. Currently used pharmaceutical grade excipients, including polymers, are primarily designed for powder compression, ens...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950795/ https://www.ncbi.nlm.nih.gov/pubmed/35329594 http://dx.doi.org/10.3390/ma15062142 |
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author | Kulinowski, Piotr Malczewski, Piotr Łaszcz, Marta Baran, Ewelina Milanowski, Bartłomiej Kuprianowicz, Mateusz Dorożyński, Przemysław |
author_facet | Kulinowski, Piotr Malczewski, Piotr Łaszcz, Marta Baran, Ewelina Milanowski, Bartłomiej Kuprianowicz, Mateusz Dorożyński, Przemysław |
author_sort | Kulinowski, Piotr |
collection | PubMed |
description | 3D printing by selective laser sintering (SLS) of high-dose drug delivery systems using pure brittle crystalline active pharmaceutical ingredients (API) is possible but impractical. Currently used pharmaceutical grade excipients, including polymers, are primarily designed for powder compression, ensuring good mechanical properties. Using these excipients for SLS usually leads to poor mechanical properties of printed tablets (printlets). Composite printlets consisting of sintered carbon-stained polyamide (PA12) and metronidazole (Met) were manufactured by SLS to overcome the issue. The printlets were characterized using DSC and IR spectroscopy together with an assessment of mechanical properties. Functional properties of the printlets, i.e., drug release in USP3 and USP4 apparatus together with flotation assessment, were evaluated. The printlets contained 80 to 90% of Met (therapeutic dose ca. 600 mg), had hardness above 40 N (comparable with compressed tablets) and were of good quality with internal porous structure, which assured flotation. The thermal stability of the composite material and the identity of its constituents were confirmed. Elastic PA12 mesh maintained the shape and structure of the printlets during drug dissolution and flotation. Laser speed and the addition of an osmotic agent in low content influenced drug release virtually not changing composition of the printlet; time to release 80% of Met varied from 0.5 to 5 h. Composite printlets consisting of elastic insoluble PA12 mesh filled with high content of crystalline Met were manufactured by 3D SLS printing. Dissolution modification by the addition of an osmotic agent was demonstrated. The study shows the need to define the requirements for excipients dedicated to 3D printing and to search for appropriate materials for this purpose. |
format | Online Article Text |
id | pubmed-8950795 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89507952022-03-26 Development of Composite, Reinforced, Highly Drug-Loaded Pharmaceutical Printlets Manufactured by Selective Laser Sintering—In Search of Relevant Excipients for Pharmaceutical 3D Printing Kulinowski, Piotr Malczewski, Piotr Łaszcz, Marta Baran, Ewelina Milanowski, Bartłomiej Kuprianowicz, Mateusz Dorożyński, Przemysław Materials (Basel) Article 3D printing by selective laser sintering (SLS) of high-dose drug delivery systems using pure brittle crystalline active pharmaceutical ingredients (API) is possible but impractical. Currently used pharmaceutical grade excipients, including polymers, are primarily designed for powder compression, ensuring good mechanical properties. Using these excipients for SLS usually leads to poor mechanical properties of printed tablets (printlets). Composite printlets consisting of sintered carbon-stained polyamide (PA12) and metronidazole (Met) were manufactured by SLS to overcome the issue. The printlets were characterized using DSC and IR spectroscopy together with an assessment of mechanical properties. Functional properties of the printlets, i.e., drug release in USP3 and USP4 apparatus together with flotation assessment, were evaluated. The printlets contained 80 to 90% of Met (therapeutic dose ca. 600 mg), had hardness above 40 N (comparable with compressed tablets) and were of good quality with internal porous structure, which assured flotation. The thermal stability of the composite material and the identity of its constituents were confirmed. Elastic PA12 mesh maintained the shape and structure of the printlets during drug dissolution and flotation. Laser speed and the addition of an osmotic agent in low content influenced drug release virtually not changing composition of the printlet; time to release 80% of Met varied from 0.5 to 5 h. Composite printlets consisting of elastic insoluble PA12 mesh filled with high content of crystalline Met were manufactured by 3D SLS printing. Dissolution modification by the addition of an osmotic agent was demonstrated. The study shows the need to define the requirements for excipients dedicated to 3D printing and to search for appropriate materials for this purpose. MDPI 2022-03-14 /pmc/articles/PMC8950795/ /pubmed/35329594 http://dx.doi.org/10.3390/ma15062142 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kulinowski, Piotr Malczewski, Piotr Łaszcz, Marta Baran, Ewelina Milanowski, Bartłomiej Kuprianowicz, Mateusz Dorożyński, Przemysław Development of Composite, Reinforced, Highly Drug-Loaded Pharmaceutical Printlets Manufactured by Selective Laser Sintering—In Search of Relevant Excipients for Pharmaceutical 3D Printing |
title | Development of Composite, Reinforced, Highly Drug-Loaded Pharmaceutical Printlets Manufactured by Selective Laser Sintering—In Search of Relevant Excipients for Pharmaceutical 3D Printing |
title_full | Development of Composite, Reinforced, Highly Drug-Loaded Pharmaceutical Printlets Manufactured by Selective Laser Sintering—In Search of Relevant Excipients for Pharmaceutical 3D Printing |
title_fullStr | Development of Composite, Reinforced, Highly Drug-Loaded Pharmaceutical Printlets Manufactured by Selective Laser Sintering—In Search of Relevant Excipients for Pharmaceutical 3D Printing |
title_full_unstemmed | Development of Composite, Reinforced, Highly Drug-Loaded Pharmaceutical Printlets Manufactured by Selective Laser Sintering—In Search of Relevant Excipients for Pharmaceutical 3D Printing |
title_short | Development of Composite, Reinforced, Highly Drug-Loaded Pharmaceutical Printlets Manufactured by Selective Laser Sintering—In Search of Relevant Excipients for Pharmaceutical 3D Printing |
title_sort | development of composite, reinforced, highly drug-loaded pharmaceutical printlets manufactured by selective laser sintering—in search of relevant excipients for pharmaceutical 3d printing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950795/ https://www.ncbi.nlm.nih.gov/pubmed/35329594 http://dx.doi.org/10.3390/ma15062142 |
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