Spray layering of human immunoglobulin G: Optimization of formulation and process parameters.
Spray layering of human immunoglobulin G: Optimization of formulation and process parameters.
复制标题
人免疫球蛋白 G 的喷雾分层：配方和工艺参数的优化。
DOI：
10.1016/j.ijpharm.2021.121238
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发表时间：
2021
影响因子：
5.8
通讯作者：
Hoag,StephenW
中科院分区：
文献类型：
--
作者：
Jiang,Bowen;Yu,Dongyue;Zhang,Yongrong;Yu,Hua;Feng,Hanping;Hoag,StephenW
喷雾成层是一种用于将药物或功能聚合物施加到载体珠上的技术;此外，它可以用作蛋白质干燥的替代方法，并在多颗粒递送系统上成层蛋白质。在本研究中，研究了喷雾分层过程中配方变量和工艺参数对人免疫球蛋白G（IgG）特性的影响。研究了聚乙烯吡咯烷酮（PVP）、海藻糖、蔗糖、L-精氨酸盐酸盐等辅料对提高IgG在喷雾成膜过程中稳定性的影响。采用三重复中心点的24完全析因设计，对蛋白质溶液进料速率、进风温度、进风流量和喷雾溶液雾化压力等工艺参数进行了研究。将PVP加入制剂中显著降低了复溶溶液的浊度，并增加了IgG回收率。添加海藻糖、蔗糖或精氨酸进一步改善了重构后的蛋白质回收率，并降低了IgG聚集的百分比。实验设计（DOE）结果显示，在研究的参数范围内，4个工艺因素对工艺产率和IgG蛋白回收率无显著影响。除雾化压力外，其他因素对单体含量均有显著影响，其中空气流量的影响最为显著。此外，进风温度对喷雾层积后IgG的体外结合活性有显著影响。通过优化配方，我们能够回收大多数喷雾分层的IgG并减少过程中的IgG聚集。DOE的研究深入了解了工艺变量如何影响喷涂层产品。
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 24full 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.