(W1130-01-04) Identifying the Operating Space and Repeatability of a Novel Filament Free FDM Printer

Purpose: Processing solid dispersion filament feedstock materials by Fused Deposition Modelling (FDM) have shown to facilitate control of drug release profiles through micro-structure design. The mechanical and rheological properties of many feedstock materials, particularly immediate release polymers, are not suitable for processing in a conventional FDM 3D printer. This study shows the operational space and performance of a novel non-filament based FDM printer, overcoming these material-based limitations.

Methods: 3D printing studies were performed with a 50 % w/w Paracetamol (PCM) – Plasdone™ S-630 formulation. Hot melt extrusion was performed as previously described ¹ on a Process 11 (Thermo Fisher, Germany) twin screw extruder. A novel, in house produced, custom made die was attached to the HME, containing a metering device that served as print head for the non-filament FDM 3D printer. The printer was equipped with a 0.4 mm diameter round nozzle. Tablets were printed at 130 °C, with a layer height of 0.2 mm using a linear print speed of 40 mm/s. Tablets were designed with an elliptical shape with a width of 12 mm, length of 20 mm, height of 5 mm and an infill of 37 %. Tablets were printed without top and bottom layers (Figure 1). The uniformity of mass and of dimensions was measured and calculated. Additional formulations containing 50% w/w PCM-Affinisol™ 15LV, 50% w/w PCM-42.5PVA-7.5 % w/w D-Sorbitol and 50% w/w Mefenamic acid – 42.5% SoluplusÒ – 7.5% w/w D-Sorbitol were also processed on the non-filament FDM printer. Complex viscosity of drug loaded extrudates was measured by performing an oscillatory temperature sweep, with a constant deformation of 0.5 % at a frequency of 1Hz. The gap setting was normal force controlled at 0.1 N.

Results: All investigated formulations were processable on the non-filament FDM printer. The upper and lower limit of complex viscosity for processing was determined. Affinisol™ 15LV and PVA formulations showed limitations in terms of API solubility across the temperature range, seen as steep increase in complex viscosity as API exceeded solubility limit in the polymer matrix. The largest process window was observed for the PCM-Affinisol™ 15LV formulation (Figure 2). In contrast, the PVA formulation showed a very small process window of 155°C only. SoluplusÒ and Plasdone™ S-630 formulations retained PCM in solution across the investigated temperature range, void of any drastic changes of complex viscosity. These formulations processed very well on the non-filament FDM printer. Repeatability of tablet prints showed good uniformity of mass (after an initial equilibration step, Figure 3) and good uniformity of dimensions.

Conclusion: Operational limits, in terms of rheological properties of formulations, have been identified for this novel non-filament FDM printer. Repeatability of tablet prints showed good uniformity of mass, complying with pharmacopeial specifications for oral solid dose forms.

References: 1. Prasad E, Robertson J, Halbert GW 2022. Mefenamic acid solid dispersions: Impact of formulation composition on processing parameters, product properties and performance. International Journal of Pharmaceutics:121505.

Acknowledgments: The authors would like to acknowledge that this work was carried out in the CMAC National Facility supported by the EPSRC (Grant ref EP/P006965/1) and by UKRPIF (UK Research Partnership Fund) award from the Higher Education Funding Council for England (HEFCE) (Grant ref HH13054). G. W. Halbert is funded by Cancer Research UK (C149/A20496). We would like to thank the National Facility team for their support in this project. We would also like to thank BASF, Ashland and Dow Chemicals for the donation of polymers.

Figure 1: 3D printed tablet with porous core: elliptical shape with dimensions of 20 mm length, 12 mm width and 5 mm height. Infill percentage 37 %. No top or bottom layer were printed.



Figure 2: Complex viscosity versus temperature for different API-polymer formulations. Red square – 50 % w/w PCM-Affinisol™ 15LV, blue triangle – 50 % w/w PCM – Polyvinylalcohol (PVA), green diamond – 50% w/w Mefenamic acid – 42.5 % w/w Soluplus – 7.5 % w/w D-Sorbitol, brown circle – 50 % w/w;



Figure 3: Tablet weight versus number of prints of a 50% w/w PCM-Plasdone™ S-630 formulation. Solid line – average weight, long dashed line – average weight + 5% EP limit, short-dashed line – average weight - 5% EP limit.