Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, United States.
Department of Microbial Pathogenesis, University of Maryland, Baltimore, MD, United States.
Int J Pharm. 2021 Dec 15;610:121238. doi: 10.1016/j.ijpharm.2021.121238. Epub 2021 Nov 5.
Spray layering is a technique used to apply drug or functional polymers onto carrier beads; in addition, it can be used as an alternative method for protein drying and to layer protein on a multiparticulate delivery system. In this study, the effects of formulation variables and process parameters on human immunoglobulin G (IgG) properties during spray layering were studied. Excipients including polyvinylpyrrolidone (PVP), trehalose, sucrose, L-arginine monohydrochloride were studied for their effects on improving IgG stability during spray layering. Process parameters including protein solution feed rate, inlet air temperature, inlet air flow rate, and atomization pressure of spray solution were studied using 2 full factorial design with three replicated center points. Adding PVP into the formulation significantly decreased the turbidity of the reconstitution solution and increased the IgG recovery. Adding trehalose, sucrose, or arginine further improved protein recovery after reconstitution and decreased the percentage of IgG aggregation. The Design of Experiments (DOE) results showed no significant effects from the four process factors on the process yield and IgG protein recovery in the range of parameters studied. All main factors except atomization pressure had significant effects on monomer percentage, among which air flow represented the most significant influence. In addition, the inlet air temperature had significant effects on the in vitro binding activity of IgG after spray layering. By optimizing the formulation, we were able to recover the most spray layered IgG and reduce the IgG aggregation during the process. The DOE studies gave insight into how process variables affect the spray layered products.
喷雾包衣是一种将药物或功能聚合物施加到载体珠上的技术；此外，它还可以用作蛋白质干燥的替代方法，并将蛋白质层压到多颗粒给药系统上。在这项研究中，研究了制剂变量和工艺参数对喷雾包衣过程中人免疫球蛋白 G（IgG）性质的影响。研究了聚维酮（PVP）、海藻糖、蔗糖、L-精氨酸单盐酸盐等赋形剂对改善喷雾包衣过程中 IgG 稳定性的影响。使用 2 个全因子设计和 3 个重复中心点研究了包括蛋白质溶液进料速率、入口空气温度、入口空气流量和喷雾溶液雾化压力在内的工艺参数。在制剂中加入 PVP 可显著降低再配制溶液的浊度并提高 IgG 的回收率。添加海藻糖、蔗糖或精氨酸可进一步提高再配制后的蛋白质回收率并降低 IgG 聚集的百分比。实验设计（DOE）结果表明，在所研究的参数范围内，四个工艺因素对工艺收率和 IgG 蛋白回收率没有显著影响。除雾化压力外，所有主要因素对单体百分比均有显著影响，其中空气流量的影响最大。此外，入口空气温度对喷雾包衣后 IgG 的体外结合活性有显著影响。通过优化配方，我们能够回收最多的喷雾包衣 IgG 并减少过程中的 IgG 聚集。DOE 研究深入了解了工艺变量如何影响喷雾包衣产品。
