The Viscosity Reduction Platform: Viscosity-Reducing Excipients for Protein Formulations

A viscosity reducing agent is a substance that decreases the viscosity of a fluid. In protein solutions, these agents work by reducing intermolecular interactions between protein molecules. This is crucial for high-concentration formulations, where increased interactions may result in clusters, high viscosities or protein aggregation. By incorporating viscosity reducing agents, manufacturers can achieve smoother, more manageable solutions that facilitate easier handling and administration, particularly in subcutaneous injections.

Using proprietary combinations of viscosity-reducing excipients that are part of the Viscosity Reduction Platform offers several benefits: reduced viscosity of the protein solution improves processability which supports more efficient downstream processing e.g., using tangential flow filtration (TFF) and allows for higher concentrations in the final formulation; specific combinations of viscosity-reducing agents help maintain protein stability even at high protein concentrations that are typically prone to aggregation; and lower viscosity solutions are easier to inject and reduce pain at the injection site supporting a better patient experience, more convenient administration options, and improved patient compliance.

Recommended viscosity-reducing additives include a range of excipients that have been shown to be effective in protein formulations and are part of our Viscosity Reduction Platform offering. Combining different functional groups, amino acids and anionic agents, is shown to achieve superior viscosity reduction and protein stability compared to the individual excipients. The best suited excipient combination needs to be chosen based on the specific protein and formulation requirements.

Choosing the right viscosity-decreasing agent involves several considerations: understanding the specific protein characteristics, defining the desired viscosity and intended route of administration (including feasible viscosity levels), and testing procedures to evaluate suitable excipients and excipient combinations that achieve the required viscosity-reducing effect. As each protein and protein formulation is different, a screening is recommended.

When reducing intermolecular interactions between different protein molecules, many viscosity-reducing excipients may also impact intramolecular interactions within the protein molecule. As the therapeutic function of the protein is highly dependent on its structure, which in turn is highly dependent on the interactions within the protein chain, any change in those intramolecular bonds may lead to (partial) unfolding and loss of protein functionality. The combinations of viscosity reducing agents that are part of the Viscosity Reduction Platform were successfully assessed for their viscosity-reducing effect and their ability to maintain protein stability.