Control of viscosity in biopharmaceutical protein formulations

Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies

“…In most VRA studies in the literature, a buffer is added to the sample in addition to the compound of interest. However, various buffer components in combination with the VRAs tested are expected to have nonadditive effects on solution viscosity [47] . In our study, we relied on the self-buffering effect of the highly concentrated protein solution [48] , which eliminated the need for an additional buffer in the formulation.…”

“…Differences in mAb viscosities are largely due to differences in hydrophobic and electrostatic interactions [47] . Therefore, hydrophobicity, charge, and charge distribution were considered in the selection of model mAbs to be representative of all therapeutic mAbs.…”

“…This implies that different factors contribute to the increase in viscosity of our model mAbs solutions. At this point, it should be noted that if the pH is lowered further (e.g., by 4 or more units below the isoelectric point), the net electrostatic effects between protein molecules alone should reduce the viscosity [47] . Therefore, the conclusions presented here cannot be generalized to the entire pH range, but only to a range of pH values around the isoelectric point for globular proteins.…”

Towards an improved prediction of concentrated antibody solution viscosity using the Huggins coefficient

“…Fitting the viscosity data of BSA solutions up to high concentrations using the Krieger-Dougherty model resulted in unrealistic maximum volume fraction values and intrinsic viscosities much higher than those measured in dilute solution 7,8 . The effective intrinsic viscosity values obtained from the fits of the Ross-Minton-Mooney model to mAb viscosity data 9,10,11 are often in excess of 10 mL g −1 , however mAb solutions more commonly have an intrinsic viscosity of between 6 and 7 mL g −1 when measured in dilute solution 12,13,14,15 . Quantitatively predicting protein solution viscosity using colloidal models is therefore impractical as parameterising the models with independent dilute solution measurements requires substantial effort but rarely captures concentrated solution behaviour.…”

Rheological Properties of Different Graphene Nanomaterials in Biological Media

“…Some works have evaluated the rheological properties of the protein solutions [ 26 , 27 , 28 ], but the main issue is to maintain the same viscosities of the physiological medium when the graphene-based nanoparticles are added, since changes in the viscosity of the protein solutions can affect to their structure. There are some works reporting the rheological behavior of nanoparticles in different media [ 29 , 30 ], in which the effect of various factors, such as preparation conditions, nanoparticle and base fluid properties, concentration, temperature, surface charge, and aggregation state on the rheological behavior of nanofluids is discussed.…”