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Katsiotis, C. S., Tikhomirov, E., Leliopoulos, C., Strømme, M. & Welch, K. (2024). Development of a simple paste for 3D printing of drug formulations containing a mesoporous material loaded with a poorly water-soluble drug. European journal of pharmaceutics and biopharmaceutics, 198, Article ID 114270.
Open this publication in new window or tab >>Development of a simple paste for 3D printing of drug formulations containing a mesoporous material loaded with a poorly water-soluble drug
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2024 (English)In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 198, article id 114270Article in journal (Refereed) Published
Abstract [en]

Poorly soluble drugs represent a substantial portion of emerging drug candidates, posing significant challenges for pharmaceutical formulators. One promising method to enhance the drug’s dissolution rate and, consequently, bioavailability involves transforming them into an amorphous state within mesoporous materials. These materials can then be seamlessly integrated into personalized drug formulations using Additive Manufacturing (AM) techniques, most commonly via Fused Deposition Modeling. Another innovative approach within the realm of AM for mesoporous material-based formulations is semi-solid extrusion (SSE). This study showcases the feasibility of a straightforward yet groundbreaking hybrid 3D printing system employing SSE to incorporate drug-loaded mesoporous magnesium carbonate (MMC) into two different drug formulations, each designed for distinct administration routes. MMC was loaded with the poorly water-soluble drug ibuprofen via a solvent evaporation method and mixed with PEG 400 as a binder and lubricant, facilitating subsequent SSE. The formulation is non-aqueous, unlike most pastes which are used for SSE, and thus is beneficial for the incorporation of poorly water-soluble drugs. The 3D printing process yielded tablets for oral administration and suppositories for rectal administration, which were then analyzed for their dissolution behavior in biorelevant media. These investigations revealed enhancements in the dissolution kinetics of the amorphous drug-loaded MMC formulations. Furthermore, an impressive drug loading of 15.3 % w/w of the total formulation was achieved, marking the highest reported loading for SSE formulations incorporating mesoporous materials to stabilize drugs in their amorphous state by a wide margin. This simple formulation containing PEG 400 also showed advantages over other aqueous formulations for SSE in that the formulations did not exhibit weight loss or changes in size or form during the curing process post-printing. These results underscore the substantial potential of this innovative hybrid 3D printing system for the development of drug dosage forms, particularly for improving the release profile of poorly water-soluble drugs.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
3D printing, Additive manufacturing, Semi Solid Extrusion, Paste, Mesoporous Magnesium Carbonate, Poorly soluble drug, Drug delivery
National Category
Pharmaceutical Sciences Other Materials Engineering
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-523789 (URN)10.1016/j.ejpb.2024.114270 (DOI)001219767500001 ()38537908 (PubMedID)
Funder
Vinnova, 2019-00029Swedish Research Council, 2019-03729
Available from: 2024-02-23 Created: 2024-02-23 Last updated: 2024-05-28Bibliographically approved
Katsiotis, C. S., Tikhomirov, E., Strømme, M., Lindh, J. & Welch, K. (2023). Combinatorial 3D printed dosage forms for a two-step and controlled drug release. European Journal of Pharmaceutical Sciences, 187, Article ID 106486.
Open this publication in new window or tab >>Combinatorial 3D printed dosage forms for a two-step and controlled drug release
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2023 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 187, article id 106486Article in journal (Refereed) Published
Abstract [en]

Fused deposition modeling (FDM) and selective laser sintering (SLS) are two of the most employed additive manufacturing (AM) techniques within the pharmaceutical research field. Despite the numerous advantages of different AM methods, their respective drawbacks have yet to be fully addressed, and therefore combinatorial systems are starting to emerge. In the present study, hybrid systems comprising SLS inserts and a two-compartment FDM shell are developed to achieve controlled release of the model drug theophylline. Via the use of SLS a partial amorphization of the drug is demonstrated, which can be advantageous in the case of poorly soluble drugs, and it is shown that sintering parameters can regulate the dosage and release kinetics of the drug from the inserts. Furthermore, via different combinations of inserts within the FDM-printed shell, various drug release patterns, such as a two-step or prolonged release, can be achieved. The study serves as a proof of concept, highlighting the advantages of combining two AM techniques, both to overcome their respective shortcomings and to develop modular and highly tunable drug delivery devices.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Fused deposition modeling, FDM, Selective laser sintering, SLS, Controlled drug release, Hybrid system
National Category
Nano Technology Pharmaceutical Sciences
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-504425 (URN)10.1016/j.ejps.2023.106486 (DOI)001028333700001 ()
Funder
Vinnova, 2019-00029Swedish Research Council, 2019-03729
Available from: 2023-06-13 Created: 2023-06-13 Last updated: 2024-02-23Bibliographically approved
Katsiotis, C. S., Tikhomirov, E., Leliopoulos, C., Strömme, M. & Welch, K. (2023). Development of a simple paste for semi-solid extrusion of different drug formulations containing a drug-loaded mesoporous material.. In: : . Paper presented at ACS Fall, San Francisco.
Open this publication in new window or tab >>Development of a simple paste for semi-solid extrusion of different drug formulations containing a drug-loaded mesoporous material.
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2023 (English)Conference paper, Oral presentation only (Refereed)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-509949 (URN)
Conference
ACS Fall, San Francisco
Available from: 2023-08-24 Created: 2023-08-24 Last updated: 2023-08-24
Katsiotis, C. S., Strømme, M. & Welch, K. (2023). Processability of mesoporous materials in fused deposition modeling for drug delivery of a model thermolabile drug. International Journal of Pharmaceutics: X, 5, Article ID 100149.
Open this publication in new window or tab >>Processability of mesoporous materials in fused deposition modeling for drug delivery of a model thermolabile drug
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
Keywords
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:nbn:se:uu:diva-491198 (URN)10.1016/j.ijpx.2022.100149 (DOI)001003803200001 ()36593988 (PubMedID)
Funder
Vinnova, 2019-00029Swedish Research Council, 2019-03729
Available from: 2022-12-19 Created: 2022-12-19 Last updated: 2024-02-23Bibliographically approved
Katsiotis, C. S., Tikhomirov, E., Leliopoulos, C., Strömme, M. & Welch, K. (2023). Semi-solid extrusion of a suppository with mesoporous material loaded with a poorly-soluble drug.. In: : . Paper presented at 4th European Conference on Pharmaceutics, Marseille, France.
Open this publication in new window or tab >>Semi-solid extrusion of a suppository with mesoporous material loaded with a poorly-soluble drug.
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2023 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-509950 (URN)
Conference
4th European Conference on Pharmaceutics, Marseille, France
Available from: 2023-08-24 Created: 2023-08-24 Last updated: 2023-08-24
Katsiotis, C. S., Strømme, M. & Welch, K. (2022). 3D printed tablets for the delivery of a poorly soluble drug through mesoporous carriers. In: : . Paper presented at 3D Pharmaprinting conference, Veldhoven, Netherlands, 30th March 2022.
Open this publication in new window or tab >>3D printed tablets for the delivery of a poorly soluble drug through mesoporous carriers
2022 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-490198 (URN)
Conference
3D Pharmaprinting conference, Veldhoven, Netherlands, 30th March 2022
Funder
Swedish Research Council
Available from: 2022-12-07 Created: 2022-12-07 Last updated: 2022-12-07Bibliographically approved
Katsaros, I., Zhou, Y., Welch, K., Xia, W., Persson, C. & Engqvist, H. (2022). Bioactive Silicon Nitride Implant Surfaces with Maintained Antibacterial Properties. Journal of Functional Biomaterials, 13(3), Article ID 129.
Open this publication in new window or tab >>Bioactive Silicon Nitride Implant Surfaces with Maintained Antibacterial Properties
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2022 (English)In: Journal of Functional Biomaterials, E-ISSN 2079-4983, Vol. 13, no 3, article id 129Article in journal (Refereed) Published
Abstract [en]

Silicon nitride (Si3N4) is a promising biomaterial, currently used in spinal fusion implants. Such implants should result in high vertebral union rates without major complications. However, pseudarthrosis remains an important complication that could lead to a need for implant replacement. Making silicon nitride implants more bioactive could lead to higher fusion rates, and reduce the incidence of pseudarthrosis. In this study, it was hypothesized that creating a highly negatively charged Si3N4 surface would enhance its bioactivity without affecting the antibacterial nature of the material. To this end, samples were thermally, chemically, and thermochemically treated. Apatite formation was examined for a 21-day immersion period as an in-vitro estimate of bioactivity. Staphylococcus aureus bacteria were inoculated on the surface of the samples, and their viability was investigated. It was found that the thermochemically and chemically treated samples exhibited enhanced bioactivity, as demonstrated by the increased spontaneous formation of apatite on their surface. All modified samples showed a reduction in the bacterial population; however, no statistically significant differences were noticed between groups. This study successfully demonstrated a simple method to improve the in vitro bioactivity of Si3N4 implants while maintaining the bacteriostatic properties.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
bioactivity, silicon nitride, surfaces, antibacterial, biomedical
National Category
Biomaterials Science Medical Materials Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-486395 (URN)10.3390/jfb13030129 (DOI)000857670200001 ()36135564 (PubMedID)
Funder
EU, Horizon 2020, 812765
Available from: 2022-10-10 Created: 2022-10-10 Last updated: 2025-02-09Bibliographically approved
Katsiotis, C. S., Strömme, M. & Welch, K. (2022). Processability of Mesoporous Materials in FDM for drug delivery of a model thermolabile drug. In: Additive Manufacturing for the Life Sciences Consortium Meeting, Uppsala, Sweden, 5-6 May, 2022: . Paper presented at Additive Manufacturing for the Life Sciences Consortium Meeting.
Open this publication in new window or tab >>Processability of Mesoporous Materials in FDM for drug delivery of a model thermolabile drug
2022 (English)In: Additive Manufacturing for the Life Sciences Consortium Meeting, Uppsala, Sweden, 5-6 May, 2022, 2022Conference paper, Poster (with or without abstract) (Other academic)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-490201 (URN)
Conference
Additive Manufacturing for the Life Sciences Consortium Meeting
Available from: 2022-12-07 Created: 2022-12-07 Last updated: 2022-12-07
Katsiotis, C. S., Åhlén, M., Strømme, M. & Welch, K. (2021). 3D-Printed Mesoporous Carrier System for Delivery of Poorly Soluble Drugs. Pharmaceutics, 13(7), Article ID 1096.
Open this publication in new window or tab >>3D-Printed Mesoporous Carrier System for Delivery of Poorly Soluble Drugs
2021 (English)In: Pharmaceutics, E-ISSN 1999-4923, Vol. 13, no 7, article id 1096Article in journal (Refereed) Published
Abstract [en]

Fused deposition modelling (FDM) is the most extensively employed 3D-printing technique used in pharmaceutical applications, and offers fast and facile formulation development of personalized dosage forms. In the present study, mesoporous materials were incorporated into a thermoplastic filament produced via hot-melt extrusion and used to produce oral dosage forms via FDM. Mesoporous materials are known to be highly effective for the amorphization and stabilization of poorly soluble drugs, and were therefore studied in order to determine their ability to enhance the drug-release properties in 3D-printed tablets. Celecoxib was selected as the model poorly soluble drug, and was loaded into mesoporous silica (MCM-41) or mesoporous magnesium carbonate. In vitro drug release tests showed that the printed tablets produced up to 3.6 and 1.5 times higher drug concentrations, and up to 4.4 and 1.9 times higher release percentages, compared to the crystalline drug or the corresponding plain drug-loaded mesoporous materials, respectively. This novel approach utilizing drug-loaded mesoporous materials in a printed tablet via FDM shows great promise in achieving personalized oral dosage forms for poorly soluble drugs.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
3D printing, fused deposition modelling, FDM, hot-melt extrusion, HME, mesoporous, mesoporous magnesium carbonate, MCM-41, poorly soluble drug, drug delivery
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-449426 (URN)10.3390/pharmaceutics13071096 (DOI)000677195200001 ()34371787 (PubMedID)
Funder
Swedish Research Council, 2019-03729
Available from: 2021-07-26 Created: 2021-07-26 Last updated: 2024-07-04Bibliographically approved
Welch, K. (2021). Additive manufacturing for drug delivery and in vivo microsensors. In: NFM (Ed.), NFM Krusenberg conference 2021: . Paper presented at NFM Krusenberg conference 2021. Uppsala: NFM
Open this publication in new window or tab >>Additive manufacturing for drug delivery and in vivo microsensors
2021 (English)In: NFM Krusenberg conference 2021 / [ed] NFM, Uppsala: NFM , 2021Conference paper, Oral presentation only (Other academic)
Place, publisher, year, edition, pages
Uppsala: NFM, 2021
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-458748 (URN)
Conference
NFM Krusenberg conference 2021
Available from: 2021-11-15 Created: 2021-11-15 Last updated: 2021-11-15
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-4543-1130

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