Some factors affecting the stability of interferon alpha 2b in solution

Area of Science:

• Biochemistry
• Protein Chemistry
• Pharmaceutical Sciences

Background:

• Recombinant human Interferon alpha 2b (rhIFN-alpha2b) is a therapeutic protein whose stability is crucial for efficacy.
• Understanding the impact of protein concentration and formulation on rhIFN-alpha2b stability is essential for drug development.

Purpose of the Study:

• To evaluate the influence of protein concentration and formulation vehicle on rhIFN-alpha2b stability.
• To determine the optimal concentration of rhIFN-alpha2b for formulation stability studies.
• To assess the biochemical stability of a liquid, albumin-free rhIFN-alpha2b formulation under various storage conditions.

Main Methods:

• Protein concentration effects on bioactivity and purity were assessed at 37°C using antiviral titration, SDS/PAGE, and RP-HPLC.
• The optimal rhIFN-alpha2b concentration (10 MIU/ml) was used to study a liquid, albumin-free formulation.
• Formulation stability was evaluated at recommended (5±3°C) and accelerated (28±2°C) storage conditions.

Main Results:

• Higher rhIFN-alpha2b concentrations (50-100 MIU/ml) protected bioactivity but decreased purity more rapidly than lower concentrations (1-10 MIU/ml).
• A concentration of 10 MIU/ml rhIFN-alpha2b was identified as optimal for formulation stability assessments.
• The liquid, albumin-free formulation exhibited acceptable biochemical stability for 2 months under accelerated conditions and for 30 months under real-time storage.

Conclusions:

• Protein concentration significantly impacts both bioactivity and purity of rhIFN-alpha2b in solution.
• A 10 MIU/ml concentration is suitable for evaluating formulation effects on rhIFN-alpha2b stability.
• The developed liquid, albumin-free formulation demonstrates long-term biochemical stability, suitable for therapeutic use.