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Processability of mesoporous materials in fused deposition modeling for drug delivery of a model thermolabile drug
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Nanotechnology and Functional Materials.ORCID iD: 0000-0002-0154-3627
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Nanotechnology and Functional Materials.ORCID iD: 0000-0002-5496-9664
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Nanotechnology and Functional Materials.ORCID iD: 0000-0003-4543-1130
2023 (English)In: International Journal of Pharmaceutics: X, E-ISSN 2590-1567, Vol. 5, article id 100149Article in journal (Refereed) Published
Abstract [en]

The incorporation of drug-loaded mesoporous materials in dosage forms prepared with fused deposition modeling (FDM) has shown the potential to solve challenges relating to additive manufacturing techniques, such as the stability of poorly-soluble drugs in the amorphous state. However, the addition of these non-melting mesoporous materials significantly affects the mechanical properties of the filament used in FDM, which in turn affects the printability of the feedstock material. Therefore, in this study a full-factorial experimental design was utilized to investigate different processing parameters of the hot melt extrusion process, their effect on various mechanical properties and the potential correlation with the filaments' printability. The thermolabile, poorly-soluble drug ibuprofen was utilized as a model drug to assess the potential of two mesoporous materials, Mesoporous Magnesium Carbonate (MMC) and a silica-based material (MCM-41), to thermally protect the loaded drug. Factorial and principal components analysis displayed a correlation between non-printable MCM-41 filaments and their mechanical properties where printable filaments had a maximum stress >7.5 MPa and a Young's modulus >83 MPa. For MMC samples there was no clear correlation, which was in large part attributed to the filaments' inconsistencies and imperfections. Finally, both mesoporous materials displayed a thermal protective feature, as the decomposition due to the thermal degradation of a significant portion of the thermolabile drug was shifted to higher temperatures post-loading. This highlights the potential capability of such a system to be implemented for thermosensitive drugs in FDM applications.

Place, publisher, year, edition, pages
Elsevier, 2023. Vol. 5, article id 100149
Keywords [en]
FDM, Hot-melt extrusion, Experimental design, Poorly-soluble drug, Mesoporous material, Thermal protection
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
URN: urn:nbn:se:uu:diva-491198DOI: 10.1016/j.ijpx.2022.100149ISI: 001003803200001PubMedID: 36593988OAI: oai:DiVA.org:uu-491198DiVA, id: diva2:1720556
Funder
Vinnova, 2019-00029Swedish Research Council, 2019-03729Available from: 2022-12-19 Created: 2022-12-19 Last updated: 2024-02-23Bibliographically approved
In thesis
1. Additive Manufacturing and Mesoporous Materials for Pharmaceutical Applications
Open this publication in new window or tab >>Additive Manufacturing and Mesoporous Materials for Pharmaceutical Applications
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Additive Manufacturing (AM), over the past decade, has evolved into a versatile technology with significant applications in pharmaceutical research. This technology enables the production of drug formulations tailored to individual patients, offering customization in both dosage and dissolution profiles. While challenges in mass production persist, 3D printing, particularly through techniques like Fused Deposition Modeling (FDM) and Semi Solid Extrusion (SSE), proves ideal for crafting smaller batches of personalized dosage forms.

A prevalent issue in drug development revolves around poor water solubility, impacting bioavailability upon oral administration. To combat this, the integration of mesoporous materials emerges as a promising strategy to enhance the dissolution of poorly water-soluble drugs. Here, the applicability of mesoporous materials is explored, as well as their incorporation with various AM techniques. Overall, the thesis dives into the investigation of combinatorial formulations, incorporating at least one 3D printed component to address specific requirements in drug delivery. 

By combining FDM with Selective Laser Sintering (SLS), a hybrid two-compartmental formulation is developed. The durable FDM-printed shell regulates buffer medium access to the contained SLS-produced inserts loaded with the drug. Varying printing parameters and insert combinations within the shell showcase the adjustability and flexibility of this hybrid approach.

Tablets with different infill percentages, containing drug-loaded mesoporous materials, are developed. Poorly water-soluble drugs are successfully amorphized within mesoporous material pores, formulated into filaments through Hot Melt Extrusion (HME), and printed via FDM. These tablets exhibit improved dissolution compared to the crystalline drug, with the dissolution behavior regulated also by the infill percentage.

The study explores the impact of drug-loaded mesoporous materials on HME-produced filament properties, studying their effect on maximum tensile strength and Young’s modulus. The relationship between these properties and filament printability is investigated. Additionally, a protective effect of mesoporous materials on drugs from thermal degradation is revealed.

For Semi Solid Extrusion (SSE) manufactured formulations, a paste is developed, comprising mesoporous material loaded with a poorly water-soluble drug and an excipient. This paste demonstrates favorable rheological properties and easy extrudability via a syringe. The formulation proves versatile for printing dosage forms for both oral and rectal administration, with the printed tablet and suppository exhibiting effective drug release.

In conclusion, this work presents valuable strategies for developing patient-tailored dosage forms, addressing specific pharmaceutical challenges like poor solubility. The integration of mesoporous materials and various 3D printing techniques showcases a promising direction for personalized medicine in the pharmaceutical field.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2024. p. 78
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 2369
Keywords
Additive Manufacturing, Fused Deposition Modelling, Semi Solid extrusion, Mesoporous materials, Poorly water soluble drugs, Drug delivery
National Category
Engineering and Technology Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-523234 (URN)978-91-513-2047-2 (ISBN)
Public defence
2024-04-12, Heinz-Otto Kreiss Lecture Hall (Å101195), Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2024-03-22 Created: 2024-02-23 Last updated: 2024-03-22

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Katsiotis, Christos S.Strømme, MariaWelch, Ken

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