Search

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.

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.

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.

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 th

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.

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 mod, Valerie R. Levine is listed as presenting and main author on the conference poster abstract page

Title on poster: Additive manufacturing of medications

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.