(M1430-01-04) Effect of Plasticizer on the Fabrication and Properties of Hot-Melt Extruded Filaments and Fused Deposition Modelling (FDM) 3D Printed Tablets

Purpose: In this study, the effect of plasticizers on the physicochemical properties of filaments and tablets was compared. Hot-melt extruded filaments and 3D printed tablets were manufactured using 5% and 10% of polyethylene glycol (PEG) 1500 and stearic acid.

Methods: Theophylline, hydroxypropyl cellulose (HPC), and plasticizer (PEG 1500 or stearic acid) were evenly mixed at a weight ratio of 20:60:10, 20:75:5 using a bench-top blender. The mixture was fed and extruded using a twin-screw extruder (Haake mini ctw, Thermo Fisher Scientific). The mixture was extruded at 155°C for all zones with a standard screw configuration at a screw speed of 25 rpm. A 1.5-1.6mm diameter, rod-shaped die was used to prepare filaments. Texture analyzer (CT3, Brookfield) was used for flexibility and brittleness evaluation. Afterward, an oval-shaped 3D printed tablets were manufactured using a 3D printer (MakerBot Replicator) and evaluated through a dissolution test.

Results: In the evaluation of physical properties of the filaments produced using the two plasticizers PEG 1500 and stearic acid, it was found that 3D printed tablets could be successfully manufactured using all of them. In both 5% and 10%, stearic acid showed a higher flexibility than PEG 1500, and 10% was higher than 5%. Hardness was higher for stearic acid than PEG 1500 at 5%, and higher for PEG 1500 than stearic acid at 10%. As a result of dissolution of the prepared 3D printed tablets, dissolution was completed within 6 hours, showing a sustained-release dissolution pattern. In water, pH 1.2 and pH 4.0, PEG 1500 showed a faster dissolution pattern than stearic acid, and the dissolution pattern tended to be faster at 10% than 5%.

Conclusion: Theophylline-loaded HPC filaments suitable for 3D printing were successfully developed to produce 3D printed sustained release tablets. This study demonstrates that the coupling of the hot-melt extrusion and FDM-based 3D printing technologies could be an effective, efficient method to develop tablets having controlled-release property. In addition, the effect of the type and ratio of the plasticizer on the dissolution was also confirmed.

Figure 1. SEM image of the filament loaded with THEO. (A) PEG 1500 (B) stearic acid.



Figure 2. Drug release profiles of the 3DP tablets; (A) distilled water and (B) pH1.2 and (C) pH4.0 Each value represents the mean ± standard deviation (n = 3).