mixed material bibliography 2025 monographic 1 Desember 2025 id Indonesia

Jurnal

ABSTRACT Mitigating protein aggregation remains a challenge in the development of biopharmaceuticals, and agitation is well known as a stress that can induce protein aggregation. However, the temperature dependence of agitation- induced aggregation is not well understood. In this study, the aggregation of an Fc-fusion protein under agitation stress was investigated at 5, 25, and 40 ◦C. Soluble and insoluble aggregates were quantified by size-exclusion liquid chromatography and flow imaging microscopy, respectively. Both the aggregation level and the aggre- gate clusters were temperature dependent. The threshold for the orbital shaking that induced protein aggregation was temperature independent. Although thermal stress at 40 ◦C increased the number of oligomers, it did not lead to a higher monomer loss in a subsequent agitation at 25 ◦C. The aggregation induced by agitation stress was suppressed by adding a surfactant or removing the vial headspace, indicating that the aggregation occurred via an interface-mediated pathway. Thus, the observed temperature dependence was attributed to the protein adsorption to the interface and the following interfacial unfolding and aggregation was affected by the tem- perature. The results emphasized the importance of temperature control during shipping to ensure the quality of drug products. Agitation stability studies at a controlled temperature also provide a deep understanding of the protein aggregation mechanism, which is important for formulation development. Thermal stress Protein aggregation Protein stability PERPUSTAKAAN SEKOLAH TINGGI ILMU KESEHATAN SAMARINDA REPOSITORY JIN0141 Perpus.Akfarsam (Jurnal Farmasi Internasional) 615 ASI 1 Desember 2025 1_December_2025.jpeg.jpeg 2358 2026-07-13 12:40:59 2026-07-13 12:50:20 machine generated