Immediate Release 3D-Printed Tablets Produced Via Fused Deposition Modeling of a Thermo-Sensitive Drug.

PURPOSE: Dissolution speeds of tablets printed via Fused Deposition Modeling (FDM) so far are significantly lower compared to powder or granule pressed immediate release tablets. The aim of this work was to print an actual immediate release tablet by choosing suitable polymers and printing designs, also taking into account lower processing temperatures (below 100°C) owing to the used model drug pantoprazole sodium. METHODS: Five different pharmaceutical grade polymers polyvinylpyrrolidone (PVP K12), polyethylene glycol 6000 (PEG 6000), Kollidon® VA64, polyethylene glycol 20,000 (PEG 20,000) and poloxamer 407 were successfully hot-melt-extruded to drug loaded filaments and printed to tablets at the required low temperatures. RESULTS: Tablets with the polymers PEG 6000 and PVP K12 and with a proportion of 10% pantoprazole sodium (w/w) demonstrated a fast drug release that was completed within 29 min or 10 min, respectively. By reducing the infill rate of PVP tablets to 50% and thereby increase the tablet porosity it was even possible to reduce the mean time for total drug release to only 3 min. CONCLUSIONS: The knowledge acquired through this work might be very beneficial for future FDM applications in the field of immediate release tablets especially with respect to thermo-sensitive drugs.

Development of permanent magnet MnAlC/polymer composites and flexible filament for bonding and 3D-printing technologies.

Searching for high-performance permanent magnets components with no limitation in shape and dimensions is highly desired to overcome the present design and manufacturing restrictions, which affect the efficiency of the final devices in energy, automotive and aerospace sectors. Advanced 3D-printing of composite materials and related technologies is an incipient route to achieve functional structures avoiding the limitations of traditional manufacturing. Gas-atomized MnAlC particles combined with polymer have been used in this work for fabricating scalable rare earth-free permanent magnet composites and extruded flexible filaments with continuous length exceeding 10 m. Solution casting has been used to synthesize homogeneous composites with tuned particles content, made of a polyethylene (PE) matrix embedding quasi-spherical particles of the ferromagnetic τ-MnAlC phase. A maximum filling factor of 86.5 and 72.3% has been obtained for the composite and the filament after extrusion, respectively. The magnetic measurements reveal no deterioration of the properties of the MnAlC particles after the composite synthesis and filament extrusion. The produced MnAlC/PE materials will serve as precursors for an efficient and scalable design and fabrication of end-products by different processing techniques (polymerized cold-compacted magnets and 3D-printing, respectively) in view of technological applications (from micro electromechanical systems to energy and transport applications).

Formulation development and process analysis of drug-loaded filaments manufactured via hot-melt extrusion for 3D-printing of medicines.

Three dimensional(3D)-printing via fused deposition modeling (FDM) allows the production of individualized solid dosage forms. However, for bringing this benefit to the patient, active pharmaceutical ingredient (API)-loaded filaments of pharmaceutical grade excipients are necessary as feedstock and have to be produced industrially. As large-scale production of API-loaded filaments has not been described in literature, this study presents a development of 3D-printable filaments, which can continuously be produced via hot-melt extrusion. Further, a combination of testing methods for mechanical resilience of filaments was applied to improve the prediction of their printability. Eudragit RL was chosen as a sustained release polymer and theophylline (30%) as thermally stable model drug. Stearic acid (7%) and polyethylene glycol 4000 (10%), were evaluated as suitable plasticizers for producing 3D-printable filaments. The two formulations were printed into solid dosage forms and analyzed regarding their dissolution profiles. This revealed that stearic acid maintained sustained release properties of the matrix whereas polyethylene glycol 4000 did not. Analysis of the continuous extrusion process was done using a design of experiments. It showed that powder feed rate and speed of the stretching device used after extrusion predominantly determine the diameter of the filament and thereby the mechanical resilience of a filament.

The effect of thermomechanical aging on the fracture resistance of additive and subtractive manufactured polyetheretherketone abutments.

OBJECTIVES: To evaluate the fracture resistance (FR) of polyetheretherketone (PEEK) abutments produced by additive and subtractive methods compared to milled zirconia abutments. METHODS: Custom abutments were designed on Ti-base abutments and produced from three different materials, namely additively manufactured PEEK (PEEK-AM), subtractively manufactured PEEK (PEEK-SM), and zirconia (N=60). PEEK-AM abutments were printed using PEEK filaments (VESTAKEEP®i4 3DF-T, Evonik Industries AG) on a M150 Medical 3D Printer (ORION AM) by fused filament fabrication (FFF). All surface treatments were carried out according to the manufacturer's instructions. All abutments were cemented on Ti-bases with hybrid abutment cement and then restored with milled zirconia crowns. Each subgroup was divided into non-aged and aged subgroups (n=10). The aged groups were subjected to thermomechanical aging (49 N, 5-55°C, 1.2 million cycles). FR tests were performed by using a universal testing machine. Data were statistically analyzed with one-way and two-way ANOVA and t-test. RESULTS: The survival rate of the specimens after aging was determined as 100%. It was found that both the material and aging had a significant effect on the FR (p<.001). There was a statistical difference among the fracture values of the groups (p<0.001). In both the aged and non-aged groups, PEEK-AM showed the statistically lowest FR, while the highest FR was seen in the zirconia group, which was significantly higher than the PEEK-SM (p<0.001). CONCLUSION: Hybrid abutments were successfully manufactured, and extrusion-based processed PEEK seems to be a good alternative to subtractive processed PEEK. However, since subtractive manufacturing still appears to be superior, further developments in additive manufacturing are needed to further improve the quality of 3D-printed PEEK parts, especially in terms of accuracy and bonding between adjacent layers. CLINICAL SIGNIFICANCE: Additively manufactured PEEK abutments have the potential to be an alternative for implant-supported restorations in the posterior region.

Influence of Manufacturing Process on the Conductivity of Material Extrusion Components: A Comparison between Filament- and Granule-Based Processes.

The additive manufacturing of components using material extrusion (MEX) enables the integration of several materials into one component, including functional structures such as electrically conductive structures. This study investigated the influence of the selected additive MEX process on the resistivity of MEX structures. Specimens were produced from filaments and granules of an electrically conductive PLA and filled with carbon nanotubes and carbon black. Specimens were produced with a full-factorial variation of the input variables: extrusion temperature, deposition speed, and production process. The resistivity of the specimens was determined by four-wire measurement. Analysis of the obtained data showed that only the extrusion temperature had a significant influence on the resistivity of the MEX specimens. Furthermore, the impact of the nozzle diameter was evaluated by comparing the results of this study with those of a previous study, with an otherwise equal experimental setup. The nozzle diameter had a significant influence on resistivity and a larger nozzle diameter reduced the mean variance by an order of magnitude. The resistivity was lower for most process parameter sets. As the manufacturing process had no significant influence on the resistivity of MEX structures, it can be selected based on other criteria, e.g., the cost of feedstock.

A simple and fast method for screening production of polymer-ceramic filaments for bone implant printing using commercial fused deposition modelling 3D printers.

3D printing is a promising technique for obtaining bone implants. However, 3D printed bone implants, especially those printed using fused deposition modelling, are still in the experimental phase despite decades of work. Research on new materials faces numerous limitations, such as reagents' cost and machines' high prices to produce filaments for 3D printing polymer-ceramic composites for fused deposition modelling. This paper presents a simple, low-cost, and fast method of obtaining polymer-ceramic filaments using apparatus consisting of parts available in a hardware store. The method's versatility for producing the filaments was demonstrated on two different biodegradable polymers - polylactic acid and polycaprolactone - and different concentrations of calcium phosphate - ß-tricalcium phosphate - in the composite, up to 50 % by weight. For screening purposes, numerous scaffolds were 3D printed from the obtained filaments on a commercial 3D printer. Structural, mechanical, and biological tests show that the 3D printed scaffolds are suitable for bone implants, as their structure, mechanical, and non-cytotoxic properties are evident. Moreover, the proposed method of composite forming is a simplification of the processes of manufacturing and researching 3D printed materials with potential applications in the regeneration of bone tissue.

A Low-Cost Process for Fabricating Reinforced 3D Printing Thermoplastic Filaments.

Low-cost desktop-sized fused deposition modeling (FDM) printers have been widely embraced by small to large-scale institutions and individuals. To further enhance their utility and increase the range of materials that they can process, this work proposes a low-cost solution that adapts to low-cost desktop-sized extruders and enables them to fabricate filaments comprising a wide range of nonorganic reinforcing particles. This solution will fill a gap in the field, as low-cost fabrication techniques for reinforced filaments have been lacking. In the proposed solution, particles are heated and deposited on thermoplastic pellets to form a coating. Coated pellets are subsequently extruded using a low-cost desktop single-screw extruder. The effectiveness of the process is demonstrated by fabricating polylactic acid (PLA) filaments reinforced with two types of reinforcements, namely, dune sand and silicon carbide. Filaments' stiffness and strength were measured, and their microstructure along their lateral and longitudinal directions were investigated. Improvements in tensile strength (up to 8%) and stiffness (up to 4.5%) were observed, but at low reinforcement levels (less than 2 wt%). Results showed that the proposed process could be used to fabricate filaments with multiple types of particles. The produced filaments were successfully used to fabricate 3D parts using a commercial desktop FDM printer.

Deformation Behavior of 3D Printed Auxetic Structures of Thermoplastic Polymers: PLA, PBAT, and Blends.

Auxetic structures have a negative Poisson's ratio and therefore expand transversely to the direction of loading instead of tapering. This unique behavior is not caused by the materials used, but by the structure, and thus offers completely new functionalities and design possibilities. As a rule, auxetic structures have a very complex geometry, which makes cost-effective production possible only by means of additive manufacturing processes. Due to the high design freedom of the strand deposition method, it makes sense to manufacture auxetic structures using this process. Therefore, in this project, polylactide acid (PLA), polybutylene adipate terephthalate (PBAT), and blends of the two polymers were produced and characterized. Filaments of the two polymers and a blend were extruded, processed into auxetic structures by strand deposition process (SDP), and investigated for their properties, primarily their Poisson's ratio. The Poisson's ratio was determined and the influence of the material on it was identified. A specific number of 5 × 5 unit cells has been found to be ideal for investigation. Dual printed specimens showed a similar auxetic behavior as the specimens made of pure PBAT. Likewise, multiple loading and unloading of the structure is possible. Furthermore, in-situ computed tomography revealed the detailed characterization of the initial state, including the warpage of the structures, damage, and traced auxetic behavior in detail.

Material Extrusion of Wool Waste/Polycaprolactone with Improved Tensile Strength and Biodegradation.

Additive manufacturing (AM) through material extrusion (MEX) is becoming increasingly popular worldwide due to its simple, sustainable and safe technique of material preparation, with minimal waste generation. This user-friendly technique is currently extensively used in diverse industries and household applications. Recently, there has been increasing attention on polycaprolactone (PCL)-based composites in MEX due to their improved biodegradability. These composites can be printed at a lower temperature, making them more energy efficient compared to commercial filaments such as acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA). Although wool is the leading protein fibre in the world and can be more compatible with PCL due to its inherent hydrophobicity, the suitability of MEX using a wool/PCL combination has not been reported previously. In the current study, waste wool/PCL composite parts were printed using the MEX technique, and rheology, thermal and tensile properties, and morphology were analysed. The impact of wool loading (10% and 20%) was investigated in relation to different filling patterns (concentric, rectilinear and gyroid). Furthermore, the impact of fibre fineness on the final material produced through MEX was investigated for the first time using two types of wool fibres with diameters of 16 µm and 24 µm. The yield strength and modulus of PCL increased with the inclusion of 10% wool, although the elongation was reduced. The crystallinity of the composites was found to be reduced with wool inclusion, though the melting point of PCL remained mostly unchanged with 10% wool inclusion, indicating better compatibility. Good miscibility and uniform structure were observed with the inclusion of 10% wool, as evidenced by rheology and morphology analysis. The impact of fibre fineness was mostly minor, though wool/PCL composites showed improved thermal stability with finer diameter of wool fibres. The printed specimens exhibited an increasing rate of biodegradation in marine water, which was correlated to the amount of wool present. Overall, the results demonstrate the practical applicability of the wool/PCL composition in MEX for the preparation of varied objects, such as containers, toys and other household and industrial items. Using wool/PCL combinations as regular plastics would provide a significant environmental advantage over the non-degradable polymers that are currently used for these purposes.

3D Printed Cellulose-Based Filaments-Processing and Mechanical Properties.

Cellulose is an abundant and sustainable material that is receiving more and more attention in different industries. In the context of additive manufacturing, it would be even more valuable. However, there are some challenges to overcome in processing cellulose-based materials. Therefore, this study used a new thermoplastic cellulose-based granulate to show its potential in filament extrusion and the fused filament fabrication printing process. Furthermore, the mechanical properties were investigated. It was shown that filaments with a suitable and uniform diameter could be produced. A parameter study for printing revealed that adhesion of the material on the bed and between layers was an issue but could be overcome with a suitable set of parameters. Tensile bars with different orientations of 0°, +/-45°, and 90° were printed and compared with injection-molded samples. It could be shown that different mechanisms (single strand breakage, shear failure) caused fracture for different printing orientations. In comparison with injection-molding, the printed parts showed lower mechanical properties (moduli of 74-95%, a tensile strength of 47-69%, and an elongation at break of 29-60%), but an improvement could be seen compared with earlier reported direct granule printing. The study showed that FFF is a suitable process for the new cellulose-based material to fabricate samples with good mechanical properties.

Additive Manufacturing of ß-Tricalcium Phosphate Components via Fused Deposition of Ceramics (FDC).

Bone defects introduced by accidents or diseases are very painful for the patient and their treatment leads to high expenses for the healthcare systems. When a bone defect reaches a critical size, the body is not able to restore this defect by itself. In this case a bone graft is required, either an autologous one taken from the patient or an artificial one made of a bioceramic material such as calcium phosphate. In this study ß-tricalcium phosphate (ß-TCP) was dispersed in a polymer matrix containing poly(lactic acid) (PLA) and poly(ethylene glycole) (PEG). These compounds were extruded to filaments, which were used for 3D printing of cylindrical scaffolds via Fused Deposition of Ceramics (FDC) technique. After shaping, the printed parts were debindered and sintered. The components combined macro- and micropores with a pore size of 1 mm and 0.01 mm, respectively, which are considered beneficial for bone healing. The compressive strength of sintered cylindrical scaffolds exceeded 72 MPa at an open porosity of 35%. The FDC approach seems promising for manufacturing patient specific bioceramic bone grafts.

Influence of High, Disperse API Load on Properties along the Fused-Layer Modeling Process Chain of Solid Dosage Forms.

In order to cope with the increasing number of multimorbid patients due to demographic changes, individualized polypill solutions must be developed. One promising tool is fused layer modeling (FLM) of dosage forms with patient-specific dose combinations and release individualization. As there are few approaches reported that systematically investigate the influence of high disperse active pharmaceutical ingredient (API) loads in filaments needed for FLM, this was the focus for the present study. Different filaments based on polyethylene oxide and hypromellose (HPMC) with different loads of theophylline as model API (up to 50 wt.%) were extruded with a twin-screw extruder and printed to dosage forms. Along the process chain, the following parameters were investigated: particle size and shape of theophylline; mechanical properties, microstructure, mass and content uniformity of filaments as well as dosage forms and the theophylline release from selected dosage forms. Especially for HPMC, increasing theophylline load enhanced the flexural strength of filaments whilst the FLM accuracy decreased inducing defects in microstructure. Theophylline load had no significant effect on the dissolution profile of HPMC-based dosage forms. Therefore, a thorough analysis of particle-induced effects is necessary to correlate mechanical properties of filaments, printability, and the dosage-and-release profile adjustment.