Nanosizing increases the specific surface of drug particles, leading to faster dissolution inside the organism and improving the bioavailability of poorly water-soluble drugs. A novel approach for the preparation of drug nanoparticles in water using chemically inert microfluidic emulsification devices is presented in this paper. A lithographic fabrication sequence was established, allowing fabrication of intersecting and coaxial channels of different depths in glass as is required for 3D flow-focusing. Fenofibrate was used as a model for active pharmaceutical ingredients with very low water solubility in the experiments. It was dissolved in ethyl acetate and emulsified in water, as allowed by the 3D flow-focusing geometry. In the thread formation regime, the drug solution turned into monodisperse droplets of sizes down to below 1 μm. Fast supersaturation occurs individually in each droplet, as the disperse phase solvent progressively diffuses into the surrounding water. Liquid antisolvent precipitation results in highly monodisperse and amorphous nanoparticles of sizes down to 128 nm which can be precisely controlled by the continuous and disperse phase pressure. By comparing optically measured droplet sizes with particle sizes by dynamic light scattering, we could confirm that exactly one particle forms in every droplet. Furthermore, a downstream on-chip concentration allowed withdrawal of major volumes of only the continuous phase fluid which enabled an increase of particle concentration by up to 250 times.

中文翻译：

---

惰性3D乳化装置，可分别沉淀和浓缩无定形药物纳米颗粒†

纳米化增加了药物颗粒的比表面积，从而导致了生物体内更快的溶解并改善了水溶性差的药物的生物利用度。本文提出了一种使用化学惰性微流乳化装置制备水中药物纳米颗粒的新方法。建立了光刻制造顺序，从而可以按照3D流动聚焦的要求在玻璃中制造相交的同轴通道和不同深度的同轴通道。非诺贝特在实验中用作水溶性非常低的活性药物成分的模型。根据3D流动聚焦几何形状的允许，将其溶于乙酸乙酯并在水中乳化。在线形成方案中，药物溶液变成尺寸小于1μm的单分散液滴。随着分散相溶剂逐渐扩散到周围的水中，每个液滴中都会快速发生过饱和。液体反溶剂沉淀导致尺寸低至128 nm的高度单分散和无定形的纳米颗粒，可以通过连续相和分散相压力精确控制。通过将光学测量的液滴尺寸与动态光散射的粒径进行比较，我们可以确认在每个液滴中仅形成一个颗粒。此外，下游的芯片上浓度仅允许抽取大体积的连续相流体，从而使颗粒浓度增加了多达250倍。液体反溶剂沉淀导致尺寸低至128 nm的高度单分散和无定形的纳米颗粒，可以通过连续相和分散相压力精确控制。通过将光学测量的液滴尺寸与动态光散射的粒径进行比较，我们可以确认在每个液滴中仅形成一个颗粒。此外，下游的芯片上浓度仅允许抽取大体积的连续相流体，从而使颗粒浓度增加了多达250倍。液体反溶剂沉淀导致尺寸低至128 nm的高度单分散和无定形的纳米颗粒，可以通过连续相和分散相压力精确控制。通过将光学测量的液滴尺寸与动态光散射的粒径进行比较，我们可以确认在每个液滴中仅形成一个颗粒。此外，下游的芯片上浓度仅允许抽取大体积的连续相流体，从而使颗粒浓度增加了多达250倍。我们可以确认在每个液滴中仅形成一个粒子。此外，下游的芯片上浓度仅允许抽取大体积的连续相流体，从而使颗粒浓度增加了多达250倍。我们可以确认在每个液滴中仅形成一个粒子。此外，下游的芯片上浓度仅允许抽取大体积的连续相流体，从而使颗粒浓度增加了多达250倍。