The Viscosity Reduction Platform: Viscosity-Reducing Excipients For Protein Formulation

By Stefan Braun, Niels Banik, Jennifer J. Widera, Alana Gouveia, Dr. Jan Gerit Brandenburg, Dr. Can Araman and Dr. Tobias Rosenkranz

One of the major obstacles in preparing highly concentrated protein formulations suitable for subcutaneous (subQ) injection is protein viscosity. The subQ application of highly concentrated protein formulations offers more convenience for patients and, potentially, a reduction in health costs. This can be achieved by minimizing the time requirement for the patient to administer therapy, e.g. by enabling self-injection at home and reducing the time commitment to do so. However, highly viscous protein solutions would require substantial force to be applied to the syringe for injection, which could cause the patient to experience a considerable amount of pain. In many instances, injectability would be impractical.

The intermolecular interactions between proteins have the same molecular origin as the intramolecular interactions that are responsible for protein structural stability. This means the excipients designed to reduce viscosity that affect protein-protein interactions can potentially destabilize proteins. Therefore, it is crucial to balance an excipient’s viscosity-reducing ability with its potential to destabilize proteins. Excipient concentration is a critical factor in managing protein stability.

Here, we assess the viscosity-reducing capacities of excipients and excipient combinations. We highlight the over-additive effect of using two excipients together and explore how the viscosity-reducing ability of excipients is influenced by pH. The findings demonstrate the impact of protein viscosity on injection force and the Viscosity Reduction Platform's ability to balance viscosity reduction with protein stability. Using a combination of two excipients at lower concentrations, instead of a single excipient at a higher concentration, offers a favorable balance between protein viscosity and stability.