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.

Monoclonal antibodies (mAb) have transformed modern medicine, offering targeted therapies for cancer, autoimmune disorders, and infectious diseases. To enhance patient convenience, subcutaneous administration is increasingly prioritized, requiring highly concentrated formulations. However, high viscosity of these formulations hinders manufacturability, injectability, and stability. Viscosity-reducing additives are a promising solution, disrupting protein-protein interactions and thereby reducing the viscosity of mAb formulations. Most promising additives are small organic electrolytes, where key properties influencing their efficacy include charge, size, and salt form. Relatively small molecules with three or more charges are most efficient, while the counter-ion provides opportunity for increased solubility and additional interactions. Our data analysis further highlights topological polar surface area and heteroatoms as significant predictors of viscosity reduction, while the role of aromatic moieties remains questionable. Another promising strategy is combining viscosity-reducing additives, which can achieve synergistic viscosity reduction while enhancing stability. Polyelectrolytes also demonstrate promising efficacy via complex formation with mAbs. Conversely, other common excipients of mAb formulations, such as sugars and surfactants, often increase viscosity of the formulation. This review provides a foundation for advancing viscosity-reducing strategies and offers actionable insights to guide future research and development of effective, patient-oriented mAb formulations.