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Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM)

Fused deposition modeling (FDM) three-dimensional (3D) printing is being increasingly explored as a direct manufacturing method to product pharmaceutical solid dosage forms. Despite its many advantages as a pharmaceutical formulation tool, it remains restricted to proof-of-concept formulations. The...

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Autores principales: Alhijjaj, Muqdad, Nasereddin, Jehad, Belton, Peter, Qi, Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956065/
https://www.ncbi.nlm.nih.gov/pubmed/31783633
http://dx.doi.org/10.3390/pharmaceutics11120633
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author Alhijjaj, Muqdad
Nasereddin, Jehad
Belton, Peter
Qi, Sheng
author_facet Alhijjaj, Muqdad
Nasereddin, Jehad
Belton, Peter
Qi, Sheng
author_sort Alhijjaj, Muqdad
collection PubMed
description Fused deposition modeling (FDM) three-dimensional (3D) printing is being increasingly explored as a direct manufacturing method to product pharmaceutical solid dosage forms. Despite its many advantages as a pharmaceutical formulation tool, it remains restricted to proof-of-concept formulations. The optimization of the printing process in order to achieve adequate precision and printing quality remains to be investigated. Demonstrating a thorough understanding of the process parameters of FDM and their impact on the quality of printed dosage forms is undoubtedly necessary should FDM advance from a proof-of-concept stage to an adapted pharmaceutical manufacturing tool. This article describes the findings of an investigation into a number of critical process parameters of FDM and their impact on quantifiable, pharmaceutically-relevant measures of quality. Polycaprolactone, one of the few polymers which is both suitable for FDM and is a GRAS (generally regarded as safe) material, was used to print internally-exposed grids, allowing examination of both their macroscopic and microstructural reproducibility of FDM. Of the measured quality parameters, dimensional authenticity of the grids was found to poorly match the target dimensions. Weights of the grids were found to significantly vary upon altering printing speed. Printing temperature showed little effect on weight. Weight uniformity per batch was found to lie within acceptable pharmaceutical quality limits. Furthermore, we report observing a microstructural distortion relating to printing temperature which we dub The First Layer Effect (FLE). Principal Component Analysis (PCA) was used to study factor interactions and revealed, among others, the existence of an interaction between weight/dosing accuracy and dimensional authenticity dictating a compromise between the two quality parameters. The Summed Standard Deviation (SSD) is proposed as a method to extract the optimum printing parameters given all the perceived quality parameters and the necessary compromises among them.
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spelling pubmed-69560652020-01-23 Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM) Alhijjaj, Muqdad Nasereddin, Jehad Belton, Peter Qi, Sheng Pharmaceutics Article Fused deposition modeling (FDM) three-dimensional (3D) printing is being increasingly explored as a direct manufacturing method to product pharmaceutical solid dosage forms. Despite its many advantages as a pharmaceutical formulation tool, it remains restricted to proof-of-concept formulations. The optimization of the printing process in order to achieve adequate precision and printing quality remains to be investigated. Demonstrating a thorough understanding of the process parameters of FDM and their impact on the quality of printed dosage forms is undoubtedly necessary should FDM advance from a proof-of-concept stage to an adapted pharmaceutical manufacturing tool. This article describes the findings of an investigation into a number of critical process parameters of FDM and their impact on quantifiable, pharmaceutically-relevant measures of quality. Polycaprolactone, one of the few polymers which is both suitable for FDM and is a GRAS (generally regarded as safe) material, was used to print internally-exposed grids, allowing examination of both their macroscopic and microstructural reproducibility of FDM. Of the measured quality parameters, dimensional authenticity of the grids was found to poorly match the target dimensions. Weights of the grids were found to significantly vary upon altering printing speed. Printing temperature showed little effect on weight. Weight uniformity per batch was found to lie within acceptable pharmaceutical quality limits. Furthermore, we report observing a microstructural distortion relating to printing temperature which we dub The First Layer Effect (FLE). Principal Component Analysis (PCA) was used to study factor interactions and revealed, among others, the existence of an interaction between weight/dosing accuracy and dimensional authenticity dictating a compromise between the two quality parameters. The Summed Standard Deviation (SSD) is proposed as a method to extract the optimum printing parameters given all the perceived quality parameters and the necessary compromises among them. MDPI 2019-11-27 /pmc/articles/PMC6956065/ /pubmed/31783633 http://dx.doi.org/10.3390/pharmaceutics11120633 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alhijjaj, Muqdad
Nasereddin, Jehad
Belton, Peter
Qi, Sheng
Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM)
title Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM)
title_full Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM)
title_fullStr Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM)
title_full_unstemmed Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM)
title_short Impact of Processing Parameters on the Quality of Pharmaceutical Solid Dosage Forms Produced by Fused Deposition Modeling (FDM)
title_sort impact of processing parameters on the quality of pharmaceutical solid dosage forms produced by fused deposition modeling (fdm)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956065/
https://www.ncbi.nlm.nih.gov/pubmed/31783633
http://dx.doi.org/10.3390/pharmaceutics11120633
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