Summary
Polysorbates are typically used in biopharmaceutical formulation stabilisation. James Humphrey, Research and Technology Specialist at Croda Pharma, outlined the challenges associated with polysorbates and presented alternative detergent strategies for biologic formulation.
It is widely known across the scientific community that polysorbates present challenges such as chemical instability, enzymatic hydrolysis, and oxidation, all of which prompt fatty acid liberation, which leads to compromised product quality.
Humphrey posed the question: How can we improve options? He outlined several options in order from low risk to high risk. The low-risk option involves a better understanding of our polysorbate, which requires understanding mechanistic behaviour, considering the impact of individual components on behaviour, and altering chemical makeup. While the high-risk end requires developing new chemical entities to overcome challenges, i.e., novel chemistry.
Croda Pharma celebrated the launch of its Super Refined Poloxamer 188. This product was initially used in cell culture applications but showed promise in improving mAb stability. It demonstrated strong stability and performance in formulation studies. Poloxamer demonstrated strong stability and performance in formulation studies, including with adalimumab, where it outperformed other detergents in maintaining drug substance integrity.
However, there are also many other products in Croda’s Range worth pointing out, including their super refined grades of polysorbate 20 and 80, which significantly reduce the likelihood of degradation. These grades remove impurities and oxygen, improving both in-pack and in-use stability, as demonstrated in studies with rituximab and histidine buffer formulations.
Humphrey also discussed studies using triglyceride lipase, which revealed complex degradation behaviours in polysorbates, with monoesters being less stable than di- and triesters. Despite degradation, residual surfactant often remains sufficient to stabilise formulations, highlighting the need for a deeper understanding.
