期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 608, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.121062
关键词
Transient cavitation; Autoinjector; Drug delivery; Multiphase flow; Syringe; Water hammer; Bubble dynamics; Pressure wave
资金
- Eli Lilly and Company
- Frederick N. Andrews Fellowship
The collapse of cavitation bubbles induced by abrupt acceleration of the syringe in an autoinjector device can lead to protein aggregation. The phenomenon is more prominent for bubbles positioned closer to the bottom wall, growing to a larger maximum radius. The strain rate induced by the bubble collapse is not large enough to unfold the proteins.
The collapse of cavitation bubbles induced by abrupt acceleration of the syringe in an autoinjector device can lead to protein aggregation. The details of bubble dynamics are investigated using an axisymmetric, threedimensional simulation with passive tracers to illustrate the transport of protein molecules. When a bubble near the syringe wall collapses, protein molecules are concentrated in the re-entrant jet, pushed towards the syringe wall, and then spread across the wall, potentially leading to protein adsorption on the syringe wall and aggregation. This phenomenon is more prominent for bubbles positioned closer to the bottom wall, growing to a larger maximum radius. The bubble's maximum radius decreases with the bubble's distance from the syringe wall and air gap pressure, and increases with an increase in liquid column height and nucleus size. The strain rate induced by the bubble collapse is not large enough to unfold the proteins. When the re-entrant jet impacts the bubble surface or syringe wall, the bubble breaks up, generating smaller bubbles with high surface concentration of protein molecules, potentially inducing aggregation in the bulk. The bubble dynamics are influenced by dimensionless distance of the nucleus from the wall, normalized by maximum bubble radius (gamma). The re-entrant jet velocity increases with gamma, while the maximum liquid pressure, typically 100 similar to 1000 bar, first decreases and then increases with gamma. For a cloud of cavitation bubbles, i.e., closely clustered bubbles, coalescence of bubbles can occur, leading to a higher peak pressure at collapse.
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