(W0930-08-49) Study and Characterization of Polyurethane Mixtures to be Employed in Direct Powder Extrusion Using Expert Systems

Purpose: Direct Powder Extrusion (DPE) is an additive manufacturing technique that relies on the feeding of a powder mixture into the printer, heating, extrusion and printing by deposition onto a building platform, layer by layer to create three-dimensional objects [1]. One of the main advantages of this technique compared to fused deposition modelling (FDM) is that it is not necessary to produce thermoplastic filaments with suitable properties before the final step of 3D printing. This fact helps to reduce time and cost in the production of drug delivery systems [2]. The aim of this work is to analyse binary and ternary powder mixtures for its potential use in DPE, as well as the resulting extruded systems obtained before the printing process. For this purpose, expert systems such as the SeDeM method or fractal analysis have been used for the characterisation of the systems and the optimisation of the process.

Methods: Binary mixtures of Anhydrous theophylline (AT) and thermoplastic polyurethane (TPU) Tecoflex^TM EG-72D and ternary mixtures adding Magnesium stearate (MS) as lubricant, were mixed for 15 min in a Turbula mixer (Willy A. Bachofen, Basel, Switzerland). Table 1 shows the composition of the different batches prepared. Rheological tests (Bulk density, Tapped density, Powder flow, Loss on drying, Inter particle porosity, Carr’s Index , Hausner Ratio, rest angle and homogeneity index) have been performed in order to apply the SeDeM expert system, according to a previous work [3]. The physical mixtures were fed into the M3DIMAKER™ pharmaceutical 3D printer (FabRx, London, UK) and were extruded at a range temperature between 135-160°. Morphological analysis of the extrudates was carried out based on the fractal analysis to measure its roughness. The analysis was performed with a stereo microscope SMZ800N (Nikon Instruments Inc., Melville, NY, USA). The mechanical properties of extruded material were evaluated using a Texture Analyser TA.XTPlus (Stable Micro Systems, Godalming, UK) following the method described by Linares et al., [4].

Results: The rheological properties of the binary mixtures assayed worsen as the percentage of AT increases. This trend is not observed for the ternary mixture in which the values of the Hausner ratio is maintained almost constant for the different batches tested due to the presence of the lubricant. All the powder mixtures could be extruded satisfactorily. The addition of MS allowed to reduce the extrusion temperature in the case of the mixtures containing 50 and 60% of AT from 150ºC and 160ºC, respectively to 135ºC. Figure 2 shows that toughness values of both binary and ternary extrudates containing the same percentage of AT were quite close between them. Thus, the inclusion of MS in ternary filaments did not provide any difference in their toughness values. Moreover, all the performed formulations, excluding those containing 60% w/w of AT, exhibited toughness values above 80 kg/mm² which is considered a critical threshold for FDM printing [5]. Ternary batches containing MS show smaller differences in the fractal dimension values compared to binary filaments, because the presence of MS softens the surface of the filament. Both ternary and binary filaments tend to have higher fractal dimension values as the percentage of AT increases, and a sharp change appears after 50% w/w of AT.

Conclusion: Both binary and ternary mixtures based in TPU have proved to be suitable to be processed by DPE. The presence of MS has demonstrated to improve the flowability of the powder mixtures studied as well as to reduce the extrusion temperature. Regarding the roughness of the extrudates, we can confirm that the presence of lubricant softens the surface of the extrudates with a higher content of AT showing all the ternary batches tested similar dimension fractal values.

References: (1) Sánchez-Guirales, S.A. et al. Pharmaceutics 2021, 13, 1583.
(2) Manjusha, A. et al. Journal of Pharmaceutical Sciences xxx 2020, 1-18.
(3) Galdón, E. et al. European Journal of Pharmaceutics and Biopharmaceutics 2016, 109, 158-164.
(4) Linares, V. et al. Pharmaceutics 2022, 14, 2298.
(5) Xu, P. et al. International Journal of Pharmaceutics, 2020 558, 119760.

Acknowledgements: This work has been supported by a PIF VI PPIT-US grant of the Universidad de Sevilla.

Table 1. Composition of the batches prepared.

Figure 1. Graphical representation of the fractal dimension versus the percentage of AT in the prepared filaments.

Figure 2. Graphical representation of the toughness versus the percentage w/w of theophylline in the filaments prepared.