| 1. |
- Chang, Ribooga, et al.
(author)
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Synthesis and characterization of sodium hafnium oxide (Na2HfO3) and its high-temperature CO2 sorption properties
- 2023
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In: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 11:14, s. 7617-7628
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Journal article (peer-reviewed)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.
(author)
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Synthesis and characterization of sodium hafnium oxide (Na2HfO3) and its high-temperature CO2 sorption properties
- 2023
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In: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 11:14, s. 7617-7628
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Journal article (peer-reviewed)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.
(author)
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Towards 3D Bioprinted Spinal Cord Organoids
- 2022
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In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:10
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Journal article (peer-reviewed)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.
(author)
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Combinatorial 3D printed dosage forms for a two-step and controlled drug release
- 2023
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In: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 187
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Journal article (peer-reviewed)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.
(author)
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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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In: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 198
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Journal article (peer-reviewed)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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| 6. |
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| 7. |
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| 8. |
- Levine, Valerie R., 1996-, et al.
(author)
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Investigation of Polymers for SLS 3D-Printing of Solid Oral Dosage Forms
- 2022
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Conference paper (peer-reviewed)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. |
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| 10. |
- Tikhomirov, Evgenii, et al.
(author)
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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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In: International Journal of Pharmaceutics. - : Elsevier. - 2590-1567. ; 6
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Journal article (peer-reviewed)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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| 11. |
- Tikhomirov, Evgenii, et al.
(author)
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In situ thermal image analysis of selective laser sintering for oral dosage form manufacturing
- 2023
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In: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier. - 0731-7085 .- 1873-264X. ; 231
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Journal article (peer-reviewed)abstract
- Additive Manufacturing (AM) is a fast-growing approach to produce personalized oral dosage forms. Even though some AM technologies are promising as alternative to conventional compounding with resulting dosage manipulation, they still suffer from a lack of quality control. Due to the high regulatory demands and standards applied to dosage forms in the case of dose accuracy and tablet properties such as friability, effective quality control is a key feature in promoting AM as a valid technology for patient-tailored medications. One of the AM techniques used is selective laser sintering, which allows for capturing the surface state layer-by-layer during the printing process. It provides the opportunity to apply non-destructive quality control based on image analysis extracting essential data at each layer of the sintering process. This work is devoted to establishing the value of data gathered via thermal image analysis for the subsequent quality control.
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| 12. |
- Tikhomirov, Evgenii, et al.
(author)
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Selective laser sintering additive manufacturing of dosage forms : Effect of powder formulation and process parameters on the physical properties of printed tablets
- 2023
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In: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 635
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Journal article (peer-reviewed)abstract
- Large batches of placebo and drug-loaded solid dosage forms were successfully fabricated using selective laser sintering (SLS) 3D printing in this study. The tablet batches were prepared using either copovidone (N-vinyl-2-pyrrolidone and vinyl acetate, PVP/VA) or polyvinyl alcohol (PVA) and activated carbon (AC) as radiation absorbent, which was added to improve the sintering of the polymer. The physical properties of the dosage forms were evaluated at different pigment concentrations (i.e., 0.5 and 1.0 wt%) and at different laser energy inputs. The mass, hardness, and friability of the tablets were found to be tunable and structures with greater mass and mechanical strength were obtained with increasing carbon concentration and energy input. Amorphization of the active pharmaceutical ingredient in the drug-loaded batches, containing 10 wt% naproxen and 1 wt% AC, was achieved in-situ during printing. Thus, amorphous solid dispersions were prepared in a single-step process and produced tablets with mass losses below 1 wt%. These findings show how the properties of dosage forms can be tuned by careful selection of the process parameters and the powder formulation. SLS 3D printing can therefore be considered to be an interesting and promising technique for the fabrication of personalized medicines.
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| 13. |
- Tikhomirov, Evgenii
(author)
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Selective laser sintering for 3D printing of medications
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Suboptimal treatment caused by inaccurate dosing of prescribed medications is a challenging issue for the pharmaceutical industry. As a result, certain groups of patients, especially pediatric patients, may suffer from a lack of specific dosage forms, leading to potential side effects. To address this issue, various manipulation techniques are being applied, such as tablet crushing, splitting, and solution preparations. Unfortunately, these methods lack accuracy and economic efficiency.3D printing technology has been considered one of the potential solutions for manufacturing limited batch dosage forms. Dosage forms produced through 3D printing can be fabricated on demand for specific patients. Furthermore, the unique properties of these dosage forms, such as API amorphization, can be adjusted due to the high tunability of the 3D printing process. The work conducted in this thesis is dedicated to investigating the potential applications of Selective Laser Sintering (SLS) and the associated aspects of this method for manufacturing solid dosage forms.The investigations into printing parameters and formulation content enabled the establishment of correlations between these factors and the properties of the final dosage forms. Higher print temperature, Laser Power Ratio, and colorant concentration led to increased mass and hardness of the dosage forms.The polymer constitutes the major portion of the formulation in terms of mass. Consequently, various grades of polymer were examined to ascertain their chemical influence on the properties of the dosage forms. The findings revealed that the type of polymer, degree of hydrolysis, and dynamic viscosity of the polymer significantly impact both the dissolution rate and API amorphization.Utilizing FDM for printing the shell component of the drug delivery device improved its durability, whereas the SLS-printed insert resulted in a faster and adjustable dissolution rate. This experiment showcased the potential of combining the advantages of each technique to produce dosage forms with additional features.A thermal image analysis device was developed and employed to monitor temperature conditions throughout the printing process. The outcomes demonstrated that the collected data could be utilized for in-process quality control objectives and serve as a dataset for machine learning algorithms. This capability allows for real-time process monitoring, defect detection, and automated process refinement.In conclusion, a comprehensive study was conducted on the application of SLS and its limitations. This study will hopefully pave the way for further discussions and the implementation of this technology.
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| 14. |
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| 15. |
- Åhlén, Michelle, et al.
(author)
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Printing for medication
- 2021
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In: Additive Manufacturing for the Life Sciences Competence Centre. Consortium Meeting Spring 2021.. - Uppsala.
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Conference paper (other academic/artistic)
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| 16. |
- Åhlén, Michelle, et al.
(author)
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Selective laser sintering 3D printing of personalized dosage forms : Effect of powder formulation and process parameters on the physical properties of the printed tablets
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Other publication (other academic/artistic)abstract
- Large batches of placebo and drug-loaded solid dosage forms were successfully fabricated using selective laser sintering (SLS) 3D printing. The tablet batches were prepared using pharmaceutical grade Plasdone S-360 (60:40 linear copolymer of N-vinyl-2-pyrrolidone and vinyl acetate) and activated carbon as the NIR-active pigment, which was added to improve the sintering of the polymer. The physical properties of the tablets were evaluated at different pigment concentrations (i.e. 0.5 and 1.0 wt.%) and at different laser energy inputs (LPR). The mass, hardness, and friability of the tablets were found to be tunable and structures of higher mass and mechanical strength were obtained with increasing carbon concentration and LPR. Amorphization of the active pharmaceutical ingredient in the drug-loaded batches, which contained 10 wt.% naproxen and 1 wt.% activated carbon, was achieved in-situ during printing and the obtained tablets showed friabilities below 1 wt.%. In conclusion, this study has shown that solid dosage forms of varying mass and mechanical strength can be manufactured using SLS 3D printing. The preparation of amorphous solid dispersions could further be prepared in a single step during the printing process thus making SLS 3D printing an interesting and promising technique for the fabrication of personalized medicines.
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| 17. |
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