RT Journal Article
SR Electronic
T1 Local Concentrating, not Shear Stress, that may Lead to Possible Instability of Protein Molecules during Syringe Injection: A Fluid Dynamic Study with Two-Phase Flow Model
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2018.009357
DO 10.5731/pdajpst.2018.009357
A1 Xing, Lei
A1 Li, Yue
A1 Li, Tonglei
YR 2019
UL http://journal.pda.org/content/early/2019/01/15/pdajpst.2018.009357.abstract
AB A two-phase flow computational fluid dynamic (CFD) model was developed to study hydrodynamic forces and protein concentration changes of a protein solution in a syringe injector. Proteins were assumed as nano-sized solid spheres commensurate with their molecular weight and suspended in aqueous environment, passing through the rapid constricted sections of the syringe. Interaction between the solid and liquid phase was taken into account and four laminar flow cases were studied under the extensional flow. Profiles of pressure, velocity, and shear stress of the different cases were examined and compared. Hydrodynamic forces on a single protein particle were further analyzed. Our results indicated that the hydrodynamic forces are too small to effect significant conformational changes of proteins. The plunger rate showed limited impact on the distribution of protein particles inside the syringe. Nonetheless, the larger velocity gradient at the connection section of the hub toward the needle resulted in considerable accumulation of proteins. Such concentrating effect may lead to protein aggregation and subsequent structural changes and will be examined in future studies.