3D printed oral theophylline doses with innovative 'radiator-like' design: Impact of polyethylene oxide (PEO) molecular weight
3D printed oral theophylline doses with innovative 'radiator-like' design: Impact of polyethylene oxide (PEO) molecular weight
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DOI：
10.1016/j.ijpharm.2019.04.017
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发表时间：
2019-06-10
影响因子：
5.8
通讯作者：
Alhnan, Mohamed A.
中科院分区：
文献类型：
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作者：
Isreb, Abdullah;Baj, Krzysztof;Alhnan, Mohamed A.
尽管聚环氧乙烷（PEO）的大量使用及其作为赋形剂在许多药品中的整合，但以前没有将这种重要的热塑性聚合物单独应用于熔融沉积成型（FDM）3D打印的报道。在这项工作中，我们研究了通过FDM 3D打印通过使用PEO作为主链聚合物与聚乙二醇（PEG）组合来制造口服剂量。将分子量为100 K、200 K、300 K、600 K或900 K的PEO与PEG 6 K（增塑剂）和模型药物（茶碱）共混。所得到的长丝被用作FDM 3D打印机的进料，以制造具有创新设计的口服剂型（ODF）。ODF被设计在一个辐射状的几何形状与连接的螺旋板和板间的间距为0.5，1，1.5或2毫米。X-射线衍射图的细丝揭示了两个独特的峰在2 θ = 7度和12度，这可以相关的茶碱晶体的衍射图案的存在。PEO和PEG的共混物产生具有可变机械阻力的长丝（对于用PEO 100 K、200 K、300 K、600 K或900 K生产的长丝，最大断裂载荷分别为357、608、649、882、781 N）。分子量为200-600 K的PEO长丝与FDM 3D打印工艺兼容。PEO分子量的进一步增加导致在打印温度下剪切粘度升高（> 10（4）Pa.S），并阻碍FDM 3D打印过程中的材料流动。辐射器状设计的平行板之间的最小间距（1 mm）被认为是促进药物从结构中释放的必要条件。这是在FDM 3D打印中使用这种广泛使用的可生物降解聚合物物种（PEO和PEG）的第一份报告。
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.