Evaluierung der Nutzbarkeit verschiedener Celluloseether zur Herstellung von peroralen Arzneiformen mittels Fused deposition modeling (FDM) 3D-Druck
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Philipps-Universität Marburg
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Abstract
The "one size fits all" approach in the medical-pharmaceutical industry relies on standardized dosages and drug formulations, failing to consider the individual needs of patients. This often results in insufficient therapeutic success or undesirable side effects. Standardized dosing is particularly problematic for drugs with a narrow therapeutic index. Furthermore, conventional pharmaceutical
manufacturing processes are optimized for mass production and lack the flexibility to produce personalized drug formulations in small batches or with variable dosages. The objective of this study was to expand the range of excipients usable in an emerging manufacturing technology for personalized drug formulations, the Fused Deposition Modeling (FDM) 3D printing process, enabling more flexible
formulation development of individualized dosage forms. Fused Deposition Modeling (FDM) is an additive manufacturing process in which a thermoplastic
material is applied layer by layer to create a three-dimensional object. A filament is heated, extruded through a nozzle, and precisely deposited onto a build platform, where it cools and solidifies. In this study, various pharmaceutical polymers (e.g., different hydroxyethyl celluloses (HEC) and hydroxypropyl celluloses (HPC)) and other excipients were evaluated for their usability in FDM. These materials were first analyzed for thermal properties (glass transition, melting, and decomposition
temperatures) and then extruded into filaments using hot-melt extrusion (HME). Subsequently, the pure filaments were examined for 3D-printing-relevant properties (e.g., flexibility, surface quality, diameter) and evaluated for printability using a 3D printer. Binary and ternary mixtures of the investigated polymers with additional plasticizing excipients were also extruded and analyzed for 3D-printing-
relevant characteristics under the same conditions. The experimental part concluded with the incorporation of two drug models (diclofenac sodium and fish sperm DNA) into quaternary mixtures. These formulations were extruded, analyzed for their usability in 3D printing, and the resulting 3D-printed tablets were evaluated for drug release from the fabricated dosage forms. The investigations showed that cellulose ethers are highly suitable for use in HME and FDM 3D
printing. They can be extruded as pure substances at moderate temperatures between 120–155 °C and offer diverse possibilities in formulation development when combined with plasticizing excipients such as glycerol or triethyl citrate, allowing extrusion even at temperatures below 100 °C. The resulting filaments exhibited good surface quality, consistent diameter, and good flexibility. However, in combination with thermosensitive DNA, used as a model for nucleic acid-based drugs, it was found that the application of cellulose ethers in 3D printing is limited. Due to the differing technical requirements of hot-melt extruders and 3D printers, the necessary 3D printing temperatures for these formulations (180 °C) were significantly higher than those for extrusion, causing thermal degradation of the drug. Conversely, formulation development for the thermally stable diclofenac sodium demonstrated the potential of HEC and HPC for 3D printing. Ternary mixtures of various HEC variants with 20% (w/w)HPC SSL and 5% (w/w) diclofenac sodium produced filaments with consistent diameter, good surface quality, and excellent mechanical properties in some cases, which were subsequently successfully printed into reproducible tablets at 195–200 °C. Additionally, the results of the drug release studies indicated that the different HEC variants enable control over the release duration and rate, making them highly suitable for controlled release systems from 3D printers with customizable dosages.
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Created: 2025Issued: 2025-03-17Updated: 2025-03-17
Faculty
Fachbereich Pharmazie
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
cellulose ether3D-Druck von Arzneimitteln3d printing of dosage forms
DFG-subjects
Fused deposition modelingCelluloseetherDNADiclofenac-NatriumFDMSchmelzschichtung3d printingPeroralArzneiform3D-Druck
DDC-Numbers
570
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Hartzke, David: Evaluierung der Nutzbarkeit verschiedener Celluloseether zur Herstellung von peroralen Arzneiformen mittels Fused deposition modeling (FDM) 3D-Druck. : Philipps-Universität Marburg 2025-03-17. DOI: https://doi.org/10.17192/z2025.0084.
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