Rheological characterization and injection forces of concentrated protein formulations: An alternative predictive model for non-Newtonian solutions

Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development

“…High viscosity of concentrated antibody formulations is the primary focus here, although we recognize that many other challenges associated with the development of high concentration antibody formulations, such as opalescence, solubility and aggregation, can also potentially delay the time to market. Additionally, this review focuses on Newtonian viscosity behavior of antibody solutions even though recent reports in literature have identified nonNewtonian behavior in certain antibody solutions 13,16,17 and the increase in viscosity due to accumulation of antibody molecules on the air/water interface. 18 …”

Challenges in the subcutaneous (SC) administration of monoclonal antibodies (mAbs)

“…At 2 mL/10 s there is considerable deviation from the Newtonian model (Figure 6.2) since highconcentration mAb solutions are non-Newtonian resulting in a decrease of viscosity at higher shear ( Figure 6.3) (Liu, Nguyen, Andya, & Shire, 2005) that yields a lower glide force. A model has been created for non-Newtonian fluids and used resulting in an excellent agreement with measured values for a Carbopol gel (Allmendinger et al, 2014). It has been suggested that the maximum force for manual injection with a syringe is about 30 N (Burckbuchler et al, 2010).…”

“…Early studies on the concentration dependence of viscosity for an IgG 1 mAb showed a strong correlation with the time required to draw 1 mL through a syringe with a 27 gauge needle (Figure 6.1). The force required to inject a Newtonian fluid with viscosity η (Pa s) with a syringe of inner radius R s equipped with a needle of length (l) and inner radius R n at a volumetric flow rate Q (mL/s) is given by the HagenPoiseuille equation (Allmendinger et al, 2014;Sutera & Skalak, 1993):…”

“…The dotted lines are presented to guide the eye and the red line shows the generally acceptable 30 N glide force for syringes. Adapted fromAllmendinger et al (2014).…”

Calculation of injection forces for highly concentrated protein solutions

“…In a recent study, Allmendinger et al employed a slightly different approach, where they did not use the shear rate at the wall, but used an average shear rate, which takes into consideration the non-linear shear rate changes throughout the needle diameter, thus coming up with the "effective shear rate" (Allmendinger et al, 2014) :…”