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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

3d printing is capable of providing dose individualization for pediatric medicines and translating the precision medicine approach into practical application. In pediatrics, dose individualization and preparation of small dosage forms is a requirement for successful therapy, which is frequently not possible due to the lack of suitable dosage forms. For precision medicine, individual characteristics of patients are considered for the selection of the best possible API in the most suitable dose with the most effective release profile to improve therapeutic outcome. 3d printing is inherently suitable for manufacturing of individualized medicines with varying dosages, sizes, release profiles and drug combinations in small batch sizes, which cannot be manufactured with traditional technologies. However, understanding of critical quality attributes and process parameters still needs to be significantly improved for this new technology. To ensure health and safety of patients, cleaning and process validation needs to be established. Additionally, adequate analytical methods for the in-process control of intermediates, regarding their printability as well as control of the final 3d printed tablets considering any risk of this new technology will be required. The PolyPrint consortium is actively working on developing novel polymers for fused deposition modeling (FDM) 3d printing, filament formulation and manufacturing development as well as optimization of the printing process, and the design of a GMP-capable FDM 3d printer. In this manuscript, the consortium shares its views on quality aspects and measures for 3d printing from drug-loaded filaments, including formulation development, the printing process, and the printed dosage forms. Additionally, engineering approaches for quality assurance during the printing process and for the final dosage form will be presented together with considerations for a GMP-capable printer design.

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.

3d printing is capable of providing dose individualization for pediatric medicines and translating the precision medicine approach into practical application. In pediatrics, dose individualization and preparation of small dosage forms is a requirement for successful therapy, which is frequently not possible due to the lack of suitable dosage forms. For precision medicine, individual characteristics of patients are considered for the selection of the best possible API in the most suitable dose with the most effective release profile to improve therapeutic outcome. 3d printing is inherently suitable for manufacturing of individualized medicines with varying dosages, sizes, release profiles and drug combinations in small batch sizes, which cannot be manufactured with traditional technologies. However, understanding of critical quality attributes and process parameters still needs to be significantly improved for this new technology. To ensure health and safety of patients, cleaning and process validation needs to be established. Additionally, adequate analytical methods for the in-process control of intermediates, regarding their printability as well as control of the final 3d printed tablets considering any risk of this new technology will be required. The PolyPrint consortium is actively working on developing novel polymers for fused deposition modeling (FDM) 3d printing, filament formulation and manufacturing development as well as optimization of the printing process, and the design of a GMP-capable FDM 3d printer. In this manuscript, the consortium shares its views on quality aspects and measures for 3d printing from drug-loaded filaments, including formulation development, the printing process, and the printed dosage forms. Additionally, engineering approaches for quality assurance during the printing process and for the final dosage form will be presented together with considerations for a GMP-capable printer design.