Genina Natalja, Holländer Jenny, Jukarainen Harri, Mäkilä Ermei, Salonen Jarno, Sandler Niklas
Pharmaceutical Sciences Laboratory, Abo Akademi University, Tykistökatu 6A, FI-20520, Turku, Finland; Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Pharmaceutical Sciences Laboratory, Abo Akademi University, Tykistökatu 6A, FI-20520, Turku, Finland.
Eur J Pharm Sci. 2016 Jul 30;90:53-63. doi: 10.1016/j.ejps.2015.11.005. Epub 2015 Nov 3.
The main purpose of this work was to investigate the printability of different grades of ethylene vinyl acetate (EVA) copolymers as new feedstock material for fused-deposition modeling (FDM™)-based 3D printing technology in fabrication of custom-made T-shaped intrauterine systems (IUS) and subcutaneous rods (SR). The goal was to select an EVA grade with optimal properties, namely vinyl acetate content, melting index, flexural modulus, for 3D printing of implantable prototypes with the drug incorporated within the entire matrix of the medical devices. Indomethacin was used as a model drug in this study. Out of the twelve tested grades of the EVA five were printable. One of them showed superior print quality and was further investigated by printing drug-loaded filaments, containing 5% and 15% indomethacin. The feedstock filaments were fabricated by hot-melt extrusion (HME) below the melting point of the drug substance and the IUS and SR were successfully printed at the temperature above the melting point of the drug. As a result, the drug substance in the printed prototypes showed to be at least partly amorphous, while the drug in the corresponding HME filaments was crystalline. This difference affected the drug release profiles from the filaments and printed prototype products: faster release from the prototypes over 30days in the in vitro tests. To conclude, this study indicates that certain grades of EVA were applicable feedstock material for 3D printing to produce drug-loaded implantable prototypes.
这项工作的主要目的是研究不同等级的乙烯-醋酸乙烯酯（EVA）共聚物作为新型原料，用于基于熔融沉积建模（FDM™）的3D打印技术制造定制的T形宫内节育系统（IUS）和皮下植入棒（SR）的可打印性。目标是选择一种具有最佳性能的EVA等级，即醋酸乙烯酯含量、熔体流动速率、弯曲模量，用于3D打印包含药物的可植入原型，药物包含在医疗设备的整个基质中。在本研究中，吲哚美辛用作模型药物。在测试的12种EVA等级中，有5种是可打印的。其中一种显示出优异的打印质量，并通过打印含有5%和15%吲哚美辛的载药长丝进行了进一步研究。原料长丝通过热熔挤出（HME）在药物熔点以下制备，IUS和SR在高于药物熔点的温度下成功打印。结果，打印原型中的药物至少部分为无定形，而相应HME长丝中的药物为结晶形。这种差异影响了长丝和打印原型产品的药物释放曲线：在体外测试中，原型在30天内释放更快。总之，本研究表明，某些等级的EVA是用于3D打印以生产载药可植入原型的适用原料。
