(T1430-08-53) Getting Sticky with It – Formulation Tenacity in 3D Printing

Purpose: 3D printing (3DP) oral solid dose forms by Fused Filament Fabrication has gained increased interest in recent years. To facilitate efficient formulation and process development, some studies developed and implemented rheological and mechanical screening tests. However, the assessment of the tenacity of formulations to the print bed have not been reported in the literature. In this study, a methodology was developed to assess the tenacity of Paracetamol (PCM) – Affinisol™ 15LV (HPMC) formulations.

Methods: Three formulations (PCM-Affinisol™ 15LV) exhibiting low (5% and 10% w/w PCM) and high (50% w/w PCM) tenacity to a 3DP bed were subject of this study [1]. Tack tests were performed on a Haake Mars III rotational rheometer equipped with a 25 mm diameter, parallel plate geometry. 500 mg of powdered sample were compacted under vacuum for 2 mins. A test sequence of an initial sample temperature axial hold (contact phase) and plate separation (removal) was performed. Method settings of temperature (190°C) and time for the initial axial hold, the applied normal force (Fn) and time during contact phase, as well as the separation (removal) height and speed (0.01 – 9.5 mm/s) were assessed. The resulting area under the curve (AUC) during plate separation was calculated indicative of the tenacity of the formulation.

Results: Long axial hold times (300 s) resulted in good reproducibility of tack test results, when plotting negative normal force versus gap height. Shorter hold times resulted in higher variability between samples (Figure 1). An increase in axial hold time was also associated with an increase in AUC. In the case of the fastest removal speed of 9.5mm/s, the negative force failed to return to the baseline, rendering the analysis invalid (Figure 2). Reducing the removal speed further increased the sharpness of the peak, with 0.1mm/s showing the sharpest peak. Further reduction of the speed to 0.01mm/s was seen as a peak broadening. Slower removal speeds of the upper plate resulted in sharper peaks, but lower AUC values. The normal force applied during the axial hold required to be high enough to promote good contact of the upper plate with the sample (0.5N - 1N), but low enough to prevent the sample running out of the gap of the sample geometry (3N). This was particularly applicable to the high drug loading formulation, due to its low complex viscosity [2].

Conclusion: The impact of method parameters on tack test measurements was assessed. A balance between axial hold time, force and temperature, as well as the removal speed need to be balanced in order for the test to be valid for a wide range of tenacity values. Tenacity (AUC) values of investigated formulations correlated well to adhesion properties during a 3DP process [1]. The test methodology can aid process development for 3DP processes.

References: [1] E. Prasad, M.T. Islam, D.J. Goodwin, A.J. Megarry, G.W. Halbert, A.J. Florence, J. Robertson, Development of a hot-melt extrusion (HME) process to produce drug loaded Affinisol™ 15LV filaments for fused filament fabrication (FFF) 3D printing, Additive Manufacturing 29 (2019), 100776.https://doi.org/10.1016/j.addma.2019.06.027.

Acknowledgements: 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 also like to thank Dow Chemicals for the donation of polymer.

Figure 1: Impact of axial hold time on data reproducibility: negative normal force (-Fn) [N] versus gap height (mm) for a 10% w/w PCM-Affinisol™ formulation. Orange lines – replicates with axial hold time 120 sec, grey lines – replicates with axial hold time 300 sec.

Figure 2: Impact of removal speed on TACK test for 5 % w/w PCM-Affinisol™ formulation at 190°C, 1N, 300 sec axial hold: negative normal force (-Fn) [N] versus gap height (mm) at removal speeds ranging from 9.5 - 0.01 mm/s. Line colours relate to removal speed: Orange - 9.5 mm/s, blue – 5mm/s, green 1 mm/s, grey 0.1 mm/s, purple – 0.01 mm/s (n=2).