Dokument: 3D Printing of Highly Loaded Amorphous Solid Dispersions for Oral Drug Delivery
| Titel: | 3D Printing of Highly Loaded Amorphous Solid Dispersions for Oral Drug Delivery | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=66423 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20240806-111921-1 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Gottschalk, Nadine [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Breitkreutz, Jörg [Gutachter] Prof. Dr. Seidlitz, Anne [Gutachter] | |||||||
| Stichwörter: | 3D printing, additive manufacturing, amorphous solid dispersion | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibung: | Three-dimensional printing has gained huge interest in the pharmaceutical sector in the past years due to its high flexibility and new opportunities for drug product development. One of the key benefits of three-dimensional printing is that, compared to traditional tablet manufacturing, tablet-like geometries can be directly printed from raw materials or an intermediate, potentially reducing the number of unit operations and number of excipients that are required to allow processing. This can be especially beneficial for the development of drug products with high dosages to reduce pill burden of the patient. In addition, the high number of poorly soluble drugs presents a major challenge in the pharmaceutical industry, which is often addressed by the formation of amorphous solid dispersion. Therefore, it is crucial to demonstrate the suitability of three-dimensional printing for this type of formulation. Two printing technologies were evaluated for the manufacturing of amorphous dosage forms in scope of this work: Fused Deposition Modeling and drop-on-powder printing.
In Fused Deposition Modeling, the three-dimensional object is created from layer-by-layer deposition of molten material through a nozzle. Filaments, a wire-like and often polymeric material, are used in this process. Filaments require specific mechanical properties, which can be difficult to achieve using solely pharmaceutical polymers as they are often very brittle. Additives such as plasticizers can be added to brittle formulations, however, this may affect the physical stability of the amorphous solid dispersion. Furthermore, amorphous solid dispersions with high drug loads offer only little design space for formulation development. In order to enable printing of brittle formulations without the use of plasticizers, one approach of this work was to modify the feeding mechanism of the printer. Modification of the feeding mechanism from gears to a piston feeding enabled the printing of very brittle formulations. Another challenge in Fused Deposition Modeling is the determination of suitable process parameters such as printing speed and nozzle temperature for each formulation. These can vary greatly, depending on the selected polymer, drug and drug content. This work introduces an empirical method to predict the aforementioned parameters with regards to mass uniformity of the finished dosage forms. Both developed methods are validated using a poorly soluble pipeline compound. In drop-on-powder printing, powder layers are fused by means of an ink or binder droplets. This technique enables manufacturing of drug products with high drug loads compared to traditional manufacturing of tablets, in which the drug load is often limited by the poor compressibility of the drug. However, drop-on-powder printing is mainly limited to well soluble compounds. To extend the scope of this technology to poorly soluble compounds, this work assessed the use of amorphous solid dispersions with high drug loads as powder material. However, the ink partially dissolves the amorphous powder particles, which may lead to recrystallization. Therefore, different inks and ink-to-powder ratios were assessed. Suitable printing conditions were identified and amorphous and physically stable tablets were successfully printed. Finally, benefits and challenges of both printing techniques to produce highly dosed as well as amorphous dosage forms were discussed considering the processability and final tablet properties. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Pharmazie » Pharmazeutische Technologie und Biopharmazie | |||||||
| Dokument erstellt am: | 06.08.2024 | |||||||
| Dateien geändert am: | 06.08.2024 | |||||||
| Promotionsantrag am: | 20.09.2023 | |||||||
| Datum der Promotion: | 08.03.2024 |
