Technische Universität Braunschweig, Institut für Pharmazeutische Technologie, Mendelssohnstr. 1, 38106 Braunschweig, Germany; Technische Universität Braunschweig, Zentrum für Pharmaverfahrenstechnik - PVZ, Franz-Liszt-Str. 35a, 38106 Braunschweig, Germany.
Technische Universität Braunschweig, Institut für Mikrotechnik, Alte Salzdahlumer Str. 203, 38124 Braunschweig, Germany; Technische Universität Braunschweig, Zentrum für Pharmaverfahrenstechnik - PVZ, Franz-Liszt-Str. 35a, 38106 Braunschweig, Germany.
Int J Pharm. 2020 Apr 15;579:119167. doi: 10.1016/j.ijpharm.2020.119167. Epub 2020 Feb 20.
Microsystems offer promising possibilities to produce nanoparticles which can be used as carriers for poorly water-soluble active substances. The aim of the present study was to compare the preparation of lipid nanoparticles by precipitation in different microsystems: A segmented-flow micromixer, a high-pressure micromixer and the commercial NanoAssemblr platform with a staggered herringbone micromixer. A batch set-up served as reference experiment. Castor oil nanoemulsions prepared with polysorbate 80 as surfactant in the aqueous phase were in the size range of 36-160 nm. The particle sizes could be reduced to 43-93 nm when the surfactant was processed via the ethanolic phase. Furthermore, glycerol monooleate nanodispersions (65-141 nm) were manufactured with poloxamer 407 added as stabilizer via the aqueous phase. Deposition of lipid material in the segmented-flow micromixer could be reduced by a modification of the design. Preparation in the high-pressure mixer and in the herringbone mixer at high total flow rates resulted in the smallest particles for castor oil emulsions, but with bimodal distributions. The particle size of glycerol monooleate dispersions was smallest when prepared in the high-pressure micromixer and in the herringbone micromixer at a higher flow rate. In conclusion, microfluidic systems can be a useful tool to produce lipid nanoparticles.
微系统为生产可作为疏水性活性物质载体的纳米粒子提供了很有前景的可能性。本研究的目的是比较在不同的微系统中通过沉淀制备脂质纳米粒子：分段流微混合器、高压微混合器和具有交错人字形微混合器的商业 NanoAssemblr 平台。分批设置用作参考实验。在水相中的聚山梨醇酯 80 作为表面活性剂制备的蓖麻油纳米乳液的粒径在 36-160nm 范围内。当表面活性剂通过乙醇相处理时，粒径可以减小到 43-93nm。此外，通过水相添加泊洛沙姆 407 作为稳定剂制造甘油单油酸纳米分散体（65-141nm）。通过对设计的修改，可以减少分段流微混合器中脂质材料的沉积。在高总流速下在高压混合器和人字形混合器中进行制备会导致蓖麻油乳液的最小颗粒，但具有双峰分布。在更高流速下在高压微混合器和人字形微混合器中制备时，甘油单油酸分散体的粒径最小。总之，微流控系统可以成为生产脂质纳米粒子的有用工具。
