School of Pharmacy, Queen's University Belfast, Belfast BT9 7BL, UK.
International Partnership for Microbicides, Silver Spring, MD 20910, USA.
Int J Pharm. 2019 Dec 15;572:118725. doi: 10.1016/j.ijpharm.2019.118725. Epub 2019 Oct 21.
Here we report the first use of an additive manufacturing (AM) technique based on high pressure material jetting of molten thermoplastic for the fabrication of dapivirine (DPV) loaded vaginal rings (VRs). The VRs are compared to those produced conventionally using injection molding (IM). VRs (outer diameter 54.0 mm, cross-sectional diameter 4.0 mm) were manufactured by either injection molding or Arburg Plastic Freeforming (APF) - a proprietary droplet deposition modelling (DDM) process, using medical grade thermoplastic polyurethanes (TPUs) loaded with 10% w/w DPV. This unique DDM process was used to produce rings of 100, 50 and 10% matrix infill density. DDM printed VRs with 10% density (57-62 mg drug load) exhibited up to seven-fold increase in DPV release compared to injection molded rings containing 190-194 mg DPV. This work has shown that DDM using the APF technique can be used to manufacture drug delivery devices of varying geometries, densities and surface areas to give precise levels of control over the drug release kinetics. This work presents a new opportunity to increase the release of poorly water-soluble compounds or to achieve desired dosing levels using lower drug loadings than those required using conventional thermoplastic processing techniques.
我们首次报告了一种基于熔融热塑性材料高压喷射的增材制造 (AM) 技术在载有双夫定（DPV）的阴道环（VR）制造中的应用。将 VR 与传统的注塑成型（IM）生产的 VR 进行了比较。VR（外径 54.0mm，横截面直径 4.0mm）采用注射成型或 Arburg Plastic Freeforming（APF）-一种专有的液滴沉积建模（DDM）工艺制造，使用载有 10% w/w DPV 的医用级热塑性聚氨酯（TPU）。这种独特的 DDM 工艺用于生产填充密度为 100%、50%和 10%的环。与含有 190-194mg DPV 的注塑成型环相比，填充密度为 10%的 DDM 打印 VR（载药量 57-62mg 药物）的 DPV 释放增加了七倍以上。这项工作表明，使用 APF 技术的 DDM 可用于制造具有不同几何形状、密度和表面积的药物输送装置，从而可以精确控制药物释放动力学。这项工作为增加难溶性化合物的释放或使用比传统热塑性加工技术所需的更低的药物负载量来实现所需的给药水平提供了新的机会。
