Increasing Protein Solubility for High-Concentration Protein Formulations using Advanced Additives

The state-of-the-art to increase protein concentration in formulations is the selection of additives to a buffer solution. These additives can be salts, amino acids, sugars, surfactants or polymers. The required condition for their addition to high concentration protein formulation (HCPF) is that these substances are approved by the Food and Drug Administration (FDA) [2]. Therefore, many possibilities exist and also combinations of additives have to be considered for HCPF. In addition, boundary conditions like viscosity and pH value have to be considered in order to administrate these solutions to a patient.

Even though high concentration antibody formulations are commercially available, only heuristic approaches exist to recommend what kind of additive shall be used for which protein [3]. Hence, the physical background for protein stabilization in high concentration is not completely understood. After the identification of suitable additives in this work that have stabilization effects on proteins in HCPF, the physical background for protein stabilization will be examined. Finally, a thermodynamic model will be applied to predict protein solubility on the basis of second osmotic virial coefficients.