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.
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Materials and Methods
The active pharmaceutical ingredient ketoprofen and all other excipients were assured from Lek d.d. stock. A number of pharmaceutical grade fillers were first screened for processability determination. Pharmatose® 200M (lactose monohydrate), Pharmatose® 125M (lactose monohydrate), and Supertab® 14 SD (spray-dried lactose monohydrate) were sourced from DFE Pharma (Goch, Germany), Avicel PH-101® (microcrystalline cellulose) from Dupont (Wilmington, DE, USA), Tabletosse® 70 (lactose monohydrate) from Meggle GmbH & Co. KG (Wasserburg am Inn, Germany), and Pearlitol® 100 SD (mannitol) from Roquette Frères (Lestrem, France). A solid binder was added to the powder blend, as this option allows for more robust dosing of pure liquid solvent via the printhead instead of introducing a dissolved binder via the binding liquid. The binder Plasdone® K- 25 (polyvinyl pyrrolidone grade K 25) was sourced from Ashland (Wilmington, DE, USA). To improve flowability of the powder blend and facilitate powder deposition in layer form, a silica-based glidant was added to the powder mixture. The glidant Syloid® 244 FP (silica) was sourced from Grace GmbH (Worms, Germany). Final powder blends were composed of 20.0% ketoprofen, 69.5% filler, 10% Plasdone® K-25, and 0.5% of Syloid® 244 FP.
Ketoprofen was sieved through a 200 μm mesh sieve to remove large particles and equate particle size with other excipients. In this way, potential particle segregation was prevented. All other excipients were sieved through a 315 μm mesh sieve to remove larger lumps and agglomerates. Powder blends were mixed in a 2 L tumbler mixer (Inversina, BioEngineering, Walt, Switzerland) for 5 min at a mixing intensity of 3.5.
Kreft, K.; Lavrič, Z.; Stanić, T.; Perhavec, P.; Dreu, R. Influence of the Binder Jetting Process Parameters and Binder Liquid Composition on the Relevant Attributes of 3D-Printed Tablets. Pharmaceutics 2022, 14, 1568. https://doi.org/10.3390/pharmaceutics14081568