Additive effects of the new viscosity-reducing and stabilizing excipients for monoclonal antibody formulation.

The subcutaneous administration of biopharmaceuticals is advantageous over intravenous administration, particularly with regard to improved patient compliance. However, in highly concentrated protein formulations lower viscosity of the formulation and stability of the protein is difficult to achieve. One approach involves using the viscosity-reducing excipients to diminish the interactions between protein molecules. In this context, the main objective of the study was to develop an optimal formulation for a model monoclonal antibody (mAb) and to evaluate new test compounds as viscosity-reducing agents. The test compounds were investigated both individually at increasing concentrations up to 200 mM and in combinations for their viscosity-reducing effect. Our results showed that all individual test compounds reduced the viscosity of the mAb formulation by more than 30 %, with reduction achieved by the six test compounds exceeding that achieved by proline (Pro). A reduction in the viscosity of the formulation below the 20 mPas threshold was achieved either by combining two test compounds or by increasing the concentration of a single compound above 25 mM. An accelerated stability study showed similar stabilization effects regardless of whether the test compounds were used alone or in combination. The percentage of aggregates was below 5 % in most formulations. These viscosity-reducing and stabilization effects corresponded to the dynamic light scattering results, which indicated that the test compounds reduced the attractive forces between the mAb molecules.