期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 111, 期 5, 页码 1370-1378出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2022.01.035
关键词
Pumping; Peristaltic pump; Tubing; Interface; Protein aggregation; Particle formation; Cavitation; Stretching; Protein(s)
Peristaltic pumping can cause protein particle formation, which is primarily attributed to heat unfolding, cavitation oxidative stress, interfacial adsorption, and tubing stretching. The study reveals that temperature and cavitation are not major factors affecting particle generation, while interfacial protein adsorption and stretching/compression of the protein film on the tubing surface are crucial elements.
Peristaltic pumping can cause protein particle formation. The expected causes were unfolding by heat in the pump head, oxidative stress by cavitation generated during roller movement, interfacial adsorption to the tubing wall and mechanical stress by stretching of the tubing itself. The pump head reached 28 degrees C during experiments stayed well below the onset of the melting point of the proteins. Thus, heat may only be a relevant root cause for proteins containing domains with very low unfolding temperature. Analysis by terephthalic acid dosimetry and protein oxidation via RP-HPLC ruled out major induction of reactive hydroxyl radicals by pumping, indicating that cavitation does not play a significant role in particle generation. Addition of surfactants suppresses protein adsorption to the tubing wall and drastically reduced protein particle formation. This indicates that interfacial protein adsorption is a key element. Repeated stretching of tubing filled with protein solution led to the formation of protein particles, demonstrating that expansion and compression of the protein film on the tubing surface is the second key component for particle formation. Thus, protein particle generation during peristaltic pumping originates from the formation of a protein film on the tubing surface which gets stretched and compressed, leading to film fragments entering the bulk solution. This interplay of protein film formation and its rupture has been also observed at liquid/liquid or liquid/air interfaces.(c) 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据