Spray Layering of Human Immunoglobulin G: Optimization of Formulation and Process Parameters.
人免疫球蛋白G的喷雾分层：制剂与工艺参数优化
📄 英文摘要 English Abstract
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 24 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.
📄 中文摘要 Chinese Abstract
📋 英文结构化总结 English Structured Summary
摘要整理
Background:
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.
Methods:
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 24 full factorial design with three replicated center points.
Results:
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.
Data Summary:
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. The 24 full factorial design with three replicated center points allowed identification of significant process effects, with air flow most significantly influencing monomer percentage and inlet air temperature affecting in vitro binding activity.
Conclusions:
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.
Practical Significance:
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. Improving IgG stability during this process has potential real-world applications in the production of stable protein-loaded multiparticulate systems.
📋 中文结构化总结 Chinese Structured Summary
背景:
喷雾包衣是一种将药物或功能性聚合物施加到载体微珠上的技术；此外，它还可作为蛋白质干燥的替代方法，并将蛋白质包衣到多颗粒递送系统中。本研究探讨了喷雾包衣过程中配方变量和工艺参数对人免疫球蛋白G（IgG）性质的影响。
方法:
研究了包括聚乙烯吡咯烷酮（PVP）、海藻糖、蔗糖、L-精氨酸一盐酸盐在内的辅料对提高喷雾包衣过程中IgG稳定性的作用。采用24全因子设计（含三个中心点重复）研究了蛋白质溶液进料速率、进气温度、进气流量和喷雾溶液雾化压力等工艺参数。
结果:
在配方中添加PVP显著降低了复溶溶液的浊度，并提高了IgG的回收率。添加海藻糖、蔗糖或精氨酸进一步提高了复溶后的蛋白质回收率，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蛋白质回收率均无显著影响。除雾化压力外，所有主要因素对单体百分比均有显著影响，其中气流的影响最为显著。此外，进气温度对喷雾包衣后IgG的体外结合活性有显著影响。
数据总结:
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。24全因子设计（含三个中心点重复）能够识别显著的工艺效应，其中气流对单体百分比的影响最为显著，而进气温度则影响体外结合活性。
结论:
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。
实际意义:
喷雾包衣是一种将药物或功能性聚合物施加到载体微珠上的技术；此外，它还可作为蛋白质干燥的替代方法，并将蛋白质包衣到多颗粒递送系统中。提高该过程中IgG的稳定性在稳定的蛋白质负载多颗粒系统的生产中具有潜在的实际应用价值。