Do not drop: mechanical shock in vials causes cavitation, protein aggregation, and particle formation.

ABSTRACT: Industry experience suggests that g-forces sustained when vials containing protein formulations are accidentally dropped can cause aggregation and particle formation. To study this phenomenon, a shock tower was used to apply controlled g-forces to glass vials containing formulations of two monoclonal antibodies and recombinant human growth hormone (rhGH). High-speed video analysis showed cavitation bubbles forming within 30 μs and subsequently collapsing in the formulations. As a result of echoing shock waves, bubbles collapsed and reappeared periodically over a millisecond time course. Fluid mechanics simulations showed low-pressure regions within the fluid where cavitation would be favored. A hydroxyphenylfluorescein assay determined that cavitation produced hydroxyl radicals. When mecha

SUBMITTER: Randolph TW 

PROVIDER: S-EPMC4312221 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature