| 1. |
- Chang, Ribooga, et al.
(författare)
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Synthesis and characterization of sodium hafnium oxide (Na2HfO3) and its high-temperature CO2 sorption properties
- 2023
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 11:14, s. 7617-7628
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Tidskriftsartikel (refereegranskat)abstract
- The CO2 sorption properties of sodium hafnium oxide (Na2HfO3) were investigated in this study. Na2HfO3 was synthesized by solid-state synthesis using Na2CO3 and HfO2 as starting materials. The solid-state synthesized Na2HfO3 appeared structurally similar to other mixed metal oxides such as Na2ZrO3, but stacking disorder appeared to be common in Na2HfO3. The synthesis conditions, including the Na : Hf ratio (between 0.5 and 1.5 : 1), synthesis temperature, time and heating rate, were investigated to optimize CO2 sorption properties of Na2HfO3. The Na2HfO3 sorbent showed comparable CO2 uptake capacity, reaction rate and excellent cycling stability compared to other metal oxide sorbents. Na2HfO3 with Na : Hf = 1 : 1 and 1.25 : 1 showed the highest CO2 uptake among all Na2HfO3 samples obtained, with a CO2 uptake capacity of around 15 wt% (at 650–800 °C). The CO2 uptake rate of NHO-1 and NHO-1.25 was fast with over 80% of the equilibrium uptake reached within 250 s. Na2HfO3 remained stable even after 100 cycles with less than 3% difference in the CO2 uptake capacity between the 1st and 100th cycles. We performed kinetic analysis on the CO2 sorption data and found that the Avrami–Erofeev model fitted the kinetic data best among the kinetic models used. Apart from sorbent optimization, we showed that 3D-printing of Na2HfO3 : HfO2 mixtures can be used to produce structured Na2HfO3 sorbents with a slightly improved CO2 uptake rate and the same CO2 uptake capacity as the powder-based solid-state synthesized Na2HfO3 sorbent.
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| 2. |
- Chang, Ribooga, et al.
(författare)
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Synthesis and characterization of sodium hafnium oxide (Na2HfO3) and its high-temperature CO2 sorption properties
- 2023
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 11:14, s. 7617-7628
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Tidskriftsartikel (refereegranskat)abstract
- The CO2 sorption properties of sodium hafnium oxide (Na2HfO3) were investigated in this study. Na2HfO3 was synthesized by solid-state synthesis using Na2CO3 and HfO2 as starting materials. The solid-state synthesized Na2HfO3 appeared structurally similar to other mixed metal oxides such as Na2ZrO3, but stacking disorder appeared to be common in Na2HfO3. The synthesis conditions, including the Na : Hf ratio (between 0.5 and 1.5 : 1), synthesis temperature, time and heating rate, were investigated to optimize CO2 sorption properties of Na2HfO3. The Na2HfO3 sorbent showed comparable CO2 uptake capacity, reaction rate and excellent cycling stability compared to other metal oxide sorbents. Na2HfO3 with Na : Hf = 1 : 1 and 1.25 : 1 showed the highest CO2 uptake among all Na2HfO3 samples obtained, with a CO2 uptake capacity of around 15 wt% (at 650–800 °C). The CO2 uptake rate of NHO-1 and NHO-1.25 was fast with over 80% of the equilibrium uptake reached within 250 s. Na2HfO3 remained stable even after 100 cycles with less than 3% difference in the CO2 uptake capacity between the 1st and 100th cycles. We performed kinetic analysis on the CO2 sorption data and found that the Avrami–Erofeev model fitted the kinetic data best among the kinetic models used. Apart from sorbent optimization, we showed that 3D-printing of Na2HfO3 : HfO2 mixtures can be used to produce structured Na2HfO3 sorbents with a slightly improved CO2 uptake rate and the same CO2 uptake capacity as the powder-based solid-state synthesized Na2HfO3 sorbent.
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| 3. |
- Han, Yilin, et al.
(författare)
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Towards 3D Bioprinted Spinal Cord Organoids
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:10
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional (3D) cultures, so-called organoids, have emerged as an attractive tool for disease modeling and therapeutic innovations. Here, we aim to determine if boundary cap neural crest stem cells (BC) can survive and differentiate in gelatin-based 3D bioprinted bioink scaffolds in order to establish an enabling technology for the fabrication of spinal cord organoids on a chip. BC previously demonstrated the ability to support survival and differentiation of co-implanted or co-cultured cells and supported motor neuron survival in excitotoxically challenged spinal cord slice cultures. We tested different combinations of bioink and cross-linked material, analyzed the survival of BC on the surface and inside the scaffolds, and then tested if human iPSC-derived neural cells (motor neuron precursors and astrocytes) can be printed with the same protocol, which was developed for BC. We showed that this protocol is applicable for human cells. Neural differentiation was more prominent in the peripheral compared to central parts of the printed construct, presumably because of easier access to differentiation-promoting factors in the medium. These findings show that the gelatin-based and enzymatically cross-linked hydrogel is a suitable bioink for building a multicellular, bioprinted spinal cord organoid, but that further measures are still required to achieve uniform neural differentiation.
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| 4. |
- Katsiotis, Christos S., et al.
(författare)
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Combinatorial 3D printed dosage forms for a two-step and controlled drug release
- 2023
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 187
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Katsiotis, Christos S., et al.
(författare)
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Development of a simple paste for 3D printing of drug formulations containing a mesoporous material loaded with a poorly water-soluble drug
- 2024
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 198
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
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| 8. |
- Levine, Valerie R., 1996-, et al.
(författare)
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Investigation of Polymers for SLS 3D-Printing of Solid Oral Dosage Forms
- 2022
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Konferensbidrag (refereegranskat)abstract
- Purpose: Selective laser sintering (SLS) for oral dosage forms is a new field still in its infancy (Fina et al., 2017). This method does, however, show promise for the application of printing oral dosage forms, particularly for small-batch scenarios or for dosages in pediatric populations, where standard medications are often not suitable due to the different size and treatment requirements of children (Ivanovska et al., 2014). In addition, 3D printing technology provides a great opportunity to speed-up clinical trials and therefore shorten development timelines. SLS printing of oral dosage forms requires specific formulation design, which includes polymers often adapted for conventional pharmaceutical usage. Current commercially available polymers are often not specifically designed for SLS printing. Therefore, there is a high need to generate application data on how to optimally print these dosage forms as well as the need for dedicated polymers suitable for this application. The development of dedicated polymers with optimized properties includes the evaluation of amphiphilic PVA grades. A direct comparison of PVA 3-82, PVA 5-74 and PVA 4-88 with other commonly used polymers is presented here. This study aims to elaborate the print parameters for a host of common pharmaceutical polymers, as well as the new PVA polymers, with regards to print temperature and laser scan speed. Additionally, this study aims to follow as closely as possible to relevant Pharmacopeia standards for tablets to show the viability of SLS as a method and find print conditions for realistic oral dosage forms.Methods: For this study PVA 3-82, PVA 5-74 and PVA 4-88 (Parteck® MXP), PVP-VA(1) (Kollidon® VA 64), PVP-VA(2) (Plasdone™) were examined. These polymers were used in formulations of 88.5% polymer, 10% API (indomethacin), 0.5% flow regulation agent (silicon dioxide colloidal), and 1% colorant (silica-based pigment, Candurin® NXT Ruby Red). A tablet design was created using Fusion 360 modelling software and translated to an STL file. A Sintratec Kit printer (2.3 W diode, λ=455 nm) was utilized to print 36 tablets per each batch, each with the same overall settings (i.e. layer height of 150 µm, 3 perimeters, hatch spacing of 50 µm). For each different polymer tested, three different temperatures and three different laser scan speeds were chosen to find optimal print conditions for each formulation; 75 ℃, 100 ℃, and 125 ℃ & 200 mm/s, 300 mm/s, and 400 mm/s, respectively. Some of the polymers, however, could not withstand the 125 ℃ print temperature, so a temperature of 112.5 ℃ was chosen instead as the upper temperature limit. After completion of printing of the tablets, characterization occurred via XRD, DSC, friability testing, mass and size analysis, HPLC, as well as dissolution.Results: During printing of the tablets, it was found that the materials PVP-VA(1) and PVP-VA(2) showed signs of the material melting together in the powder bed at 125 ℃. Therefore, the temperature of upper limit for these formulations was 112.5 ℃. Upon evaluation, the most robust tablets per batch were generally printed at higher temperature (without exceeding the appropriate temperature window for each polymer) and lower laser scan speed. These tablets generally appeared better sintered together, had less signs of crystallinity with XRD and DSC analysis, and performed better in friability testing. The mass deviations for these samples also passed mass criteria of Pharmacopeia standards in several cases. Dissolution studies showed a strong solubility enhancement of PVA based formulation compared to the crystalline drug compound.Conclusion: The print ranges for these polymers commonly used in the pharmaceutical industry, as well as the newly developed PVA grades PVA 3-82 and PVA 5-74, could be individually defined based on variations in temperature and laser scan speed. Generally, trends of higher temperatures within the print range and lower laser scan speeds showed the best results upon characterization and visual inspection. These tablets were less powdery on the surface, more fitting to the desired shape of the intended tablet (i.e. less shifting between layers), and darker in color (implying a more complete sintering). The application of SLS printing in the area of solubility enhancement is a great step into further advancing the technology and allowing the development of patient-centered medication.
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| 9. |
- Tikhomirov, Evgenii, et al.
(författare)
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Additive Manufacturing of Medications
- 2022
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Ingår i: NanoBSR Symposium, Tällberg, June 14-17, 2022..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Tikhomirov, Evgenii, et al.
(författare)
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Impact of polymer chemistry on critical quality attributes of selective laser sintering 3D printed solid oral dosage forms
- 2023
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 2590-1567. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to investigate the influence of polymer chemistry on the properties of oral dosage forms produced using selective laser sintering (SLS). The dosage forms were printed using different grades of polyvinyl alcohol or copovidone in combination with indomethacin as the active pharmaceutical ingredient. The properties of the printed structures were assessed according to European Pharmacopoeia guidelines at different printing temperatures and laser scanning speeds in order to determine the suitable printing parameters.The results of the study indicate that the chemical properties of the polymers, such as dynamic viscosity, degree of hydrolyzation, and molecular weight, have significant impact on drug release and kinetics. Drug release rate and supersaturation can be modulated by selecting the appropriate polymer type. Furthermore, the physical properties of the dosage forms printed under the same settings are influenced by the selected polymer type, which determines the ideal manufacturing settings.This study demonstrates how the chemical properties of the polymer can determine the appropriate choice of manufacturing settings and the final properties of oral dosage forms produced using SLS.
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