Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices

被引:193
作者
Genina, Natalja [1 ,2 ]
Hollander, Jenny [1 ]
Jukarainen, Harri [3 ]
Makila, Ermei [4 ]
Salonen, Jarno [4 ]
Sandler, Niklas [1 ]
机构
[1] Abo Akad Univ, Pharmaceut Sci Lab, Tykistokatu 6A, FI-20520 Turku, Finland
[2] Univ Copenhagen, Dept Pharm, Univ Pk 2, DK-2100 Copenhagen, Denmark
[3] Bayer AG, Espoo, Finland
[4] Univ Turku, Lab Ind Phys, Dept Phys & Astron, Vesilinnantie 5, FI-20014 Turku, Finland
关键词
3D printing; EVA copolymer; Hot-melt extrusion; Controlled drug delivery; Medical devices; Indomethacin; FUSED DEPOSITION; SUSTAINED-RELEASE; MELT EXTRUSION; VAGINAL RINGS; IMPLANTS; INDOMETHACIN; FABRICATION; SYSTEMS;
D O I
10.1016/j.ejps.2015.11.005
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
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 (TM))-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 30 days 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. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:53 / 63
页数:11
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