4.7 Article

3D printed oral theophylline doses with innovative 'radiator-like' design: Impact of polyethylene oxide (PEO) molecular weight

期刊

INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 564, 期 -, 页码 98-105

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ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2019.04.017

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Personalised medicine; Additive manufacturing; Complex structures; Tablets; Patient-specific; Structural design

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Despite the abundant use of polyethylene oxides (PEOs) and their integration as an excipient in numerous pharmaceutical products, there have been no previous reports of applying this important thermoplastic polymer species alone to fused deposition modelling (FDM) 3D printing. In this work, we have investigated the manufacture of oral doses via FDM 3D printing by employing PEOs as a backbone polymer in combination with polyethylene glycol (PEG). Blends of PEO (molecular weight 100 K, 200 K, 300 K, 600 K or 900 K) with PEG 6 K (plasticiser) and a model drug (theophylline) were hot-melt extruded. The resultant filaments were used as a feed for FDM 3D printer to fabricate oral dosage forms (ODFs) with innovative designs. ODFs were designed in a radiator-like geometry with connected paralleled plates and inter-plate spacing of either 0.5, 1, 1.5 or 2 mm. X-ray diffraction patterns of the filaments revealed the presence of two distinctive peaks at 2 theta = 7 degrees and 12 degrees, which can be correlated to the diffraction pattern of theophylline crystals. Blends of PEO and PEG yielded filaments of variable mechanically resistance (maximum load at break of 357, 608, 649, 882, 781 N for filament produced with PEO 100 K, 200 K, 300 K, 600 K or 900 K, respectively). Filaments of PEO at a molecular weight of 200-600 K were compatible with FDM 3D printing process. Further increase in PEO molecular weight resulted in elevated shear viscosity (> 10(4) Pa.S) at the printing temperature and hindered material flow during FDM 3D printing process. A minimal spacing (1 mm) between parallel plates of the radiator-like design deemed essential to boost drug release from the structure. This is the first report of utilising this widely used biodegradable polymer species (PEOs and PEG) in FDM 3D printing.

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