Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045.
Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309.
J Pharm Sci. 2018 Jul;107(7):1852-1857. doi: 10.1016/j.xphs.2018.03.016. Epub 2018 Mar 27.
In this study, we investigated the potential roles of nanoparticles (<100 nm) and submicron (100-1000 nm) particles in the formation of microparticles (>1000 nm) in protein formulations under some pharmaceutically relevant stress conditions. Exposure of intravenous immunoglobulin solutions to the interface-associated stresses of freeze-thawing or agitation resulted in relatively large increases in microparticle concentrations, which depended directly on the levels of pre-existing nano- and submicron particles. Thus, agglomeration of nanoparticles and submicron particles appears to play a role in microparticle formation under these stresses. In contrast, increases in microparticle concentrations during quiescent incubation at elevated temperatures were independent of the initial nano- and submicron particle concentrations in solution.
在这项研究中，我们研究了纳米颗粒（<100nm）和亚微米颗粒（100-1000nm）在某些药物相关应激条件下蛋白质制剂中形成大于 1000nm 的微粒的潜在作用。静脉注射免疫球蛋白溶液暴露于冻融或搅拌等与界面相关的应激条件下，会导致微粒浓度相对较大增加，这直接取决于预先存在的纳米和亚微米颗粒的水平。因此，纳米颗粒和亚微米颗粒的团聚似乎在这些应激下微粒形成中起作用。相比之下，在升高温度下的静止孵育过程中，微粒浓度的增加与溶液中初始纳米和亚微米颗粒浓度无关。
