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Development of an efficient single-step freeze-drying cycle for protein formulations
1Department of Formulation and Pharmaceutical Development, Synergen, Inc., Boulder, Colorado 80303, USA.
Pharmaceutical Research
|June 1, 1995
Summary
This study optimized freeze-drying for recombinant human interleukin-1 receptor antagonist (rhIL-1ra) using glycine and sucrose. A novel single-step cycle achieved 0.4% moisture content in 6 hours, enhancing stability.
Area of Science:
- Pharmaceutical Sciences
- Biotechnology
- Materials Science
Background:
- Recombinant human interleukin-1 receptor antagonist (rhIL-1ra) requires stable formulations for therapeutic use.
- Freeze-drying (lyophilization) is a critical process for stabilizing protein-based therapeutics.
- Excipients like glycine and sucrose are commonly used in lyophilization formulations.
Purpose of the Study:
- To develop an efficient freeze-drying cycle for rhIL-1ra formulations containing glycine and sucrose.
- To optimize lyophilization parameters for improved stability and reduced cycle time.
Main Methods:
- Characterization of frozen formulations using thermal analysis (e.g., differential scanning calorimetry).
- Investigation of lyophilization process parameters (shelf temperature, chamber pressure) influencing ice sublimation rate.
- Monitoring of product temperature and formulation's glass transition temperature (Tg') during drying.
Main Results:
- Thermal analysis revealed that glycine's metastable glass could be devitrified by controlled warming to -15°C.
- Ice sublimation rate was directly proportional to the difference between product vapor pressure (PO) and chamber pressure (PC).
- Maintaining product temperature below Tg' while maximizing PO, using higher shelf temperatures and lower chamber pressures, accelerated sublimation.
Conclusions:
- A single-step freeze-drying cycle was successfully developed by integrating primary and secondary drying phases.
- Product temperature was controlled below Tg' during primary drying by adjusting chamber pressure, followed by natural increase to shelf temperature for secondary drying.
- The optimized cycle achieved a low moisture content (0.4%) for 1 ml of rhIL-1ra formulation within 6 hours, demonstrating efficiency and successful stabilization.