配方成分对trastuzumab稳定性的影响
Aziz Ahmad1, Hesham Refaat2, Sanghati Bhattacharya2
1Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, United States.
International journal of pharmaceutics
|January 27, 2025
概括
配方成分在压力期间显著影响单克隆抗体聚合,而不是 conformational 稳定性. 糖配方在冷干燥后增加了可溶性聚合物,而醇配方在后增加了不可溶性聚合物.
科学领域:
- 生物制药配方 生物制药配方
- 蛋白质的稳定性和聚合.
背景情况:
- 生物相似单克隆抗体通常与创新产品的配方不同.
- 药物配方对药物产品在压力下稳定性的影响尚未完全理解.
研究的目的:
- 评估不同配方在常见应力下如何影响trastuzumab (单克隆抗体) 的结构稳定性和聚合.
- 了解配方成分在减轻或加剧压力引起的变化的作用.
主要方法:
- 特拉斯图祖马布 (药物和药物制品) 用不同的稳定剂 (糖糖,酸盐,三糖) 配制.
- 配方经过冷解,冷干燥和振动应力.
- 分析了形态稳定性和聚合 (可溶和不可溶).
主要成果:
- 所有配方均表现出良好的形状稳定性,能够承受被测试的应力.
- 在含糖的配方中,冷干燥增加了可溶性聚合物.
- 动增加了含醇配方中的不溶性聚合物,可能是由于表面活性剂的缺失.
- 三醇表现出度独立的稳定性.
结论:
- 配方成分对单克隆抗体聚合的影响要大于对形状稳定性的影响.
- 生物制剂的有效配方设计需要仔细考虑稳定性和聚合行为.
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