Department of Pharmacy and Pharmaceutical Technology, Universidad de Sevilla, C/Profesor García González 2, 41012 Seville, Spain.
Department of Pharmacy and Pharmaceutical Technology, Universidad de Sevilla, C/Profesor García González 2, 41012 Seville, Spain.
Eur J Pharm Biopharm. 2019 Jan;134:138-143. doi: 10.1016/j.ejpb.2018.11.021. Epub 2018 Nov 24.
Three-dimensional printing has become a feasible manufacturing technique for pharmaceutical products providing cheap and accurate freeform systems with a great potential for personalized-dose drugs. Fused Deposition Modeling (FDM) highlights among other 3D technologies due to its low cost and easy to operate but, until now, it has the drawbacks of the low drug loaded and the impossibility to print thermosensitive drugs. So, intermediate processes such as hot melt extrusion are frequently associated with FDM. Here, pharmaceutical dosage forms have been manufactured for the first time with a 3D printer combining two different printing technologies: FDM and injection volume filling (IVF), performing customized extruded scaffolds in which a liquid or semisolid system can be injected at room temperature. A model drug and a pH-sensitive polymer were successfully incorporated during the construction of the extruded backbone of the systems, called printfills (printed systems filled with a liquid or semisolid). SEM microphotographs of printfills show the sealing of the structure in the perimeter and the homogeneity of the colonic film formed in the upper side. Thus, the addition of the pH-sensitive polymer does not need an additional process in a fluidized bed or coating pan. Results from drug release studies performed at different pH confirm the ability of printfills for colon-specific drug delivery. Therefore, IVF technology complements FDM, solving its main limitations providing an easy, automatized and versatile technology to manufacture tailored drug delivery platforms, avoiding other intermediate processes.
三维打印已成为制药产品的一种可行制造技术，提供了廉价且精确的自由成型系统，具有很大的个性化剂量药物潜力。熔融沉积成型（FDM）在其他 3D 技术中脱颖而出，因为它成本低、易于操作，但到目前为止，它存在载药量低和无法打印热敏药物的缺点。因此，热熔融挤出等中间过程经常与 FDM 结合使用。在这里，首次使用 3D 打印机结合两种不同的打印技术制造了药物剂型：FDM 和注射体积填充（IVF），可以在室温下注射液体或半固态系统，以执行定制的挤出支架。成功地在系统的挤出骨架的构建过程中加入了模型药物和 pH 敏感聚合物，该系统称为 printfills（填充有液体或半固体的打印系统）。printfills 的 SEM 显微照片显示了结构周边的密封和在上侧形成的结肠膜的均匀性。因此，pH 敏感聚合物的添加不需要在流化床或包衣锅中进行额外的处理。在不同 pH 值下进行的药物释放研究结果证实了 printfills 用于结肠特异性药物递送的能力。因此，IVF 技术补充了 FDM，解决了其主要限制，提供了一种简单、自动化和通用的技术来制造定制的药物输送平台，避免了其他中间过程。
