The potential of three-dimensional printing for pediatric oral solid dosage forms.

Pediatric patients often require individualized dosing of medicine due to their unique pharmacokinetic and developmental characteristics. Current methods for tailoring the dose of pediatric medications, such as tablet splitting or compounding liquid formulations, have limitations in terms of dosing accuracy and palatability. This paper explores the potential of 3D printing as a solution to address the challenges and provide tailored doses of medication for each pediatric patient. The technological overview of 3D printing is discussed, highlighting various 3D printing technologies and their suitability for pharmaceutical applications. Several individualization options with the potential to improve adherence are discussed, such as individualized dosage, custom release kinetics, tablet shape, and palatability. To integrate the preparation of 3D printed medication at the point of care, a decentralized manufacturing model is proposed. In this setup, pharmaceutical companies would routinely provide materials and instructions for 3D printing, while specialized compounding centers or hospital pharmacies perform the printing of medication. In addition, clinical opportunities of 3D printing for dose-finding trials are emphasized. On the other hand, current challenges in adequate dosing, regulatory compliance, adherence to quality standards, and maintenance of intellectual property need to be addressed for 3D printing to close the gap in personalized oral medication.

Correlating mechanical and rheological filament properties to processability and quality of 3D printed tablets using multiple linear regression.

Filament formulation for FDM is a challenging and time-consuming process. Several pharmaceutical polymers are not feedable on their own. Due to inadequate filament formulation, 3D printed tablets can also exhibit poor uniformity of tablet attributes. To better understand filament formulation process, 23 filaments were prepared with the polymer mixing approach. To yield processable filaments, brittle and pliable polymers were combined. A 20 % addition of a pliable polymer to a brittle one resulted in filament processability and vice versa. Predictive statistical models for filament processability and uniformity of tablet attributes were established based on the mechanical and rheological properties of filaments. 15 input variables were correlated to 9 responses, which represent filament processability and tablet properties, by using multiple linear regression approach. Filament stiffness, assessed by indentation, and its square term were the only variables that determined the filament's feedability. However, the resulting model is equipment-specific since different feeding mechanism exert different forces on the filaments. Additional models with good predictive power (R2pred > 0.50) were established for tablet width uniformity, drug release uniformity, tablet disintegration time uniformity and occurrence of disintegration, which are equipment-independent outputs. Therefore, the obtained model outcomes could be used in other research endeavours.

Influence of fused deposition modelling printing parameters on tablet disintegration times: a design of experiments study.

Despite the importance of process parameters in the printing of solid dosage forms using fused deposition modelling (FDM) technology, the field is still poorly explored. A design of experiment study was conducted to understand the complete set of process parameters of a custom developed FDM 3D printer and their influence on tablet disintegration time. Nine settings in the Simplify 3D printing process design software were evaluated with further experimental investigation conducted on the influence of infill percentage, infill pattern, nozzle diameter, and layer height. The percentage of infill was identified as the most impactful parameter, as increasing it parabolically affected the increase of disintegration time. Furthermore, a larger nozzle diameter prolonged tablet disintegration, since thicker extruded strands are generated through wider nozzles during the printing process. Three infill patterns were selected for in-depth analysis, demonstrating the clear importance of the geometry of the internal structure to resist mechanical stress during the disintegration test. Lastly, layer height did not influence the disintegration time. A statistical model with accurate fit (R 2 = 0.928) and predictability (Q 2 = 0.847) was created. In addition, only the infill pattern and layer height influenced both the uniformity of mass and uniformity of the disintegration time, which demonstrates the robustness of the printing process.

Influence of the Binder Jetting Process Parameters and Binder Liquid Composition on the Relevant Attributes of 3D-Printed Tablets.

Binder jetting has the potential to revolutionize the way we produce medicine. However, tablets produced by binder jetting technology can be quite fragile and hard to handle. In this study, the printing process and ink composition were examined to optimize the mechanical properties of tablets. A model formulation containing the ketoprofen drug was developed and used as a base for optimization. Firstly, important printing parameters were identified with a fractional factorial design. Saturation and layer height critically influenced selected tablet properties. Relevant process parameters were optimized for tablet mechanical strength by using the D-optimization DoE approach. The best mechanical properties were achieved when saturation was set to 1 and layer height to 150 µm. On the other hand, binder ink composition did not appear to impact tablet mechanical strength as much as process parameters did. Three ethanol-water mixtures were tested at three tablet strength levels and no definitive conclusions could be drawn. The binder jetting process can be wasteful, especially if the unbound powder cannot be reused. To determine the suitability of powder blend recycling, the ketoprofen content was measured for 27 subsequent batches of tablets. While the trendline did indicate a slight reduction in ketoprofen content, the powder blend reuse can nevertheless be employed.