title: Ethylene vinyl acetate (EVA) as a new drug carrier for 3D printed medical drug delivery devices.
abstract: 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.
authors.affiliation: Pharmaceutical Sciences Laboratory, Abo Akademi University, Tykistökatu 6A, FI-20520, Turku, Finland; Department of Pharmacy, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Natalja
authors.initials: N
authors.lastname: Genina
authors.affiliation: Pharmaceutical Sciences Laboratory, Abo Akademi University, Tykistökatu 6A, FI-20520, Turku, Finland.
authors.forename: Jenny
authors.initials: J
authors.lastname: Holländer
authors.affiliation: Bayer AG, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Jukarainen
authors.affiliation: Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, Vesilinnantie 5, FI-20014, Turku, Finland.
authors.forename: Ermei
authors.initials: E
authors.lastname: Mäkilä
authors.affiliation: Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, Vesilinnantie 5, FI-20014, Turku, Finland.
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.affiliation: Pharmaceutical Sciences Laboratory, Abo Akademi University, Tykistökatu 6A, FI-20520, Turku, Finland.
authors.forename: Niklas
authors.initials: N
authors.lastname: Sandler
mesh_terms: D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry; D007434:Intrauterine Devices; D011145:Polyvinyls / Q000737:chemistry*; D066330:Printing, Three-Dimensional / Q000295:instrumentation*; D012212:Rheology; D014783:Viscosity; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D007213:Indomethacin
keywords: 3D printing; Controlled drug delivery; EVA copolymer; Hot-melt extrusion; Indomethacin; Medical devices