Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544.
Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544.
J Pharm Sci. 2018 Sep;107(9):2465-2471. doi: 10.1016/j.xphs.2018.05.003. Epub 2018 May 15.
Flash NanoPrecipitation is a scalable approach to generate polymeric nanoparticles using rapid micromixing in specially designed geometries such as a confined impinging jets mixer or a Multi-Inlet Vortex Mixer (MIVM). A major limitation of formulation screening using the MIVM is that a single run requires tens of milligrams of the therapeutic. To overcome this, we have developed a scaled-down version of the MIVM, requiring as little as 0.2 mg of therapeutic, for formulation screening. The redesigned mixer can then be attached to pumps for scale-up of the identified formulation. It was shown that Reynolds number allowed accurate scaling between the 2 MIVM designs. The utility of the small-scale MIVM for formulation development was demonstrated through the encapsulation of a number of hydrophilic macromolecules using inverse Flash NanoPrecipitation with target loadings as high as 50% by mass.
闪式纳米沉淀是一种可扩展的方法，可通过在特殊设计的几何形状（如受限冲击射流混合器或多入口涡旋混合器（MIVM））中快速微混合来生成聚合物纳米颗粒。使用 MIVM 进行配方筛选的主要限制是单次运行需要数十毫克的治疗剂。为了克服这一问题，我们开发了一种 MIVM 的缩小版，用于配方筛选，只需 0.2 毫克的治疗剂。然后可以将重新设计的混合器连接到泵上，以扩大已确定的配方。结果表明，雷诺数允许在这两种 MIVM 设计之间进行精确缩放。通过使用反向闪式纳米沉淀技术，将许多亲水性大分子包封在纳米颗粒中，最高载药量高达 50%（质量分数），证明了小尺寸 MIVM 在制剂开发中的实用性。
