A Thermofluor Screen For The Rational Formulation Of Injectable Therapeutic Protein Solutions

By Jacob Poxon

Therapeutic proteins intended for parenteral delivery are highly susceptible to denaturation and aggregation, processes that threaten drug efficacy and patient safety. Injectable buffers are essential to stabilise proteins by enhancing non-covalent interactions, shielding against environmental stressors, and minimising chemical instabilities such as oxidation, reduction, and deamidation. Traditional buffer formulation techniques — such as buffer exchange and circular dichroism — can provide valuable insight but are resource-intensive, low-throughput, and poorly suited to early formulation screening.

Thermal shift fluorimetry (thermofluor) offers a rapid, low-volume, and cost-effective alternative to guide formulation design. In this study, a high-throughput 96-well thermofluor array was constructed using excipients approved for parenteral administration. A model monoclonal antibody (mAb1) was screened across a panel of physiologically compatible buffers and stabilising additives.

The results highlight thermofluor screening as a versatile and efficient platform for rational formulation of injectable biologics. Broader adoption of this method could accelerate stable drug product development while reducing cost and resource burden — now is the time to integrate thermofluor into protein formulation workflows.