High-Concentration Formulation

Additional characterization challenges in the course of high-concentration formulation of monoclonal antibodies and other biotherapeutics include understanding the interplay of weak interactions, and viscosity.

Protein-Protein interactions

Weak protein-protein interactions may not be important at low concentrations, and so are not necessarily reflected in dilute-condition parameters such as k D, but come to dominate at high concentration. CG-MALS uniquely addresses these complex interactions through a theoretical framework known as the Minton-Chatelier formalism. This technique distinguishes attractive interactions causing aggregation, opalescence and viscosity, from repulsive interactions which may impact measurements but have little effect on stability.

Viscosity screening

Viscosity is both indicative of colloidal stability, and an important parameter on its own since high viscosity impacts manufacturability and deliverability of the final product. DLS readily determines viscosity of concentrated protein solutions using tracer beads. The DynaPro Plate Reader can evaluate the viscosity of samples as small as 10 µL in a few seconds, measuring thousands of conditions per day in order to screen for ideal viscosity-reducing excipients.

Turbidity or opalescence measurements

Turbidity becomes important in high-concentration formulations due to interactions between different species in solution resulting in opalescence and poor product quality. Turbidity of a solution is interpolated from a turbidity calibration plot. A quartz cuvette is calibrated against a series of turbidity standards, and the turbidity of a solution subsequently measured in that cuvette is calculated and displayed in the data table in nephelometric units (NTU). Visit our turbidity page to learn more.