Quality of FDM 3D Printed Medicines for Pediatrics: Considerations for Formulation Development, Filament Extrusion, Printing Process and Printer Design

Abstract

Abstract3d 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.

3D Printing of Pediatric Medication: The End of Bad Tasting Oral Liquids?—A Scoping Review

“…Cost-effectiveness is imperative to successfully implement 3D-printed drug products, as it enhances patient accessibility. Furthermore, regulatory guidelines and non-destructive quality control requirements are yet to be established for 3D-printed drug products, but are needed to ensure user-safety, legal protection and waste-reduction [39,78,79]. The regulatory viewpoint might depend on the starting point of the 3D printing process.…”

Creating Acceptable Tablets 3D (CAT 3D): A Feasibility Study to Evaluate the Acceptability of 3D Printed Tablets in Children and Young People

“…There has been a global recognition for the need to improve access to patient-appropriate formulations for paediatrics. While there has been a lot of research that covers the technical challenge of producing DFs using 3DP and its quality control [ 36 , 37 , 38 ], the acceptability of the 3D printed DFs requires investigation. The study also highlights the potential of CYP themselves as co-designers of personalised DFs that could be produced by 3DP to meet their own needs of acceptable and age-appropriate medicines.…”

Embedding a Sensitive Liquid-Core Waveguide UV Detector into an HPLC-UV System for Simultaneous Quantification of Differently Dosed Active Ingredients during Drug Release

“…The desired filament diameter was achieved using a belt hauled-off unit of a winder (Brabender, Duisburg, Germany) with a belt speed of 0.8 m/min, and the filament was pulled through a roll-system with four 360° air flow ring nozzles (Super Air Wipe, Exair, Cincinnati, OH, USA) for active cooling of the melt. With a laser-based diameter measurement module (Laser 2025 T, Sikora, Bremen, Germany), we continuously measured and logged the filament diameter during the process with a readout rate of 1 Hz to ensure diameter homogeneity [ 33 ] of PVA-P and EVA-LD-BZ filaments. The screw speed was set to 20 rpm and powder feed rate was set to 2 g/min.…”