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实现药物植入物的高分辨率 3D 打印——相关材料性能和工艺参数的整体分析。

Toward high-resolution 3D-printing of pharmaceutical implants - A holistic analysis of relevant material properties and process parameters.

机构信息

Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria; Institute of Pharmaceutical Sciences, Pharmaceutical Technology and Biopharmacy, University of Graz, Universitaetsplatz 1, 8010 Graz, Austria.

Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010 Graz, Austria.

出版信息

Int J Pharm. 2024 Jul 20;660:124356. doi: 10.1016/j.ijpharm.2024.124356. Epub 2024 Jun 17.

Abstract

In this work, filament-based 3D-printing, the most widely used sub-category of material extrusion additive manufacturing (MEAM), is presented as a promising manufacturing platform for the production of subcutaneous implants. Print nozzle diameters as small as 100 µm were utilized demonstrating MEAM of advanced porous internal structures at the given cylindrical implant geometry of 2 mm × 40 mm. The bottlenecks related to high-resolution MEAM of subcutaneous implants are systematically analyzed and the print process is optimized accordingly. Custom synthesized biodegradable phase-separated poly(ether ester) multiblock copolymers exhibiting appropriate melt viscosity at comparatively low printing temperatures of 135 °C and 165 °C were utilized as 3D-printing feedstock. The print process was optimized to minimize thermomechanical polymer degradation by employing print speeds of 30 mm∙s in combination with a nozzle diameter of 150 µm at layer heights of 110 µm. These results portray the basis for further development of subcutaneous implantable drug delivery systems where drug release profiles can be tailored through the adaption of the internal implant structure, which cannot be achieved using existing manufacturing techniques.

摘要

在这项工作中,纤维状 3D 打印作为材料挤出增材制造(MEAM)中应用最广泛的子类别,被展示为生产皮下植入物的有前途的制造平台。使用直径小至 100 µm 的打印喷嘴,在给定的 2mm×40mm 的圆柱形植入物几何形状下展示了先进的多孔内部结构的 MEAM。系统地分析了与高分辨率皮下植入物 MEAM 相关的瓶颈,并相应地优化了打印工艺。使用定制合成的可生物降解的相分离聚(醚酯)嵌段共聚物作为 3D 打印原料,其在相对较低的打印温度 135°C 和 165°C 下具有适当的熔体粘度。通过采用 30mm·s 的打印速度并结合 150µm 的喷嘴直径和 110µm 的层厚,优化了打印工艺以最小化热机械聚合物降解。这些结果为进一步开发皮下植入药物输送系统奠定了基础,通过适应内部植入物结构,可以定制药物释放曲线,而这是现有制造技术无法实现的。

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