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Mannitol-sucrose mixtures--versatile formulations for protein lyophilization.
Robert E Johnson1, Carol F Kirchhoff, Henry T Gaud
1Pharmacia Corporation, Research and Development, 4901 Searle Parkway, Skokie, Illinois 60077, USA. robert.e.johnson@pharmacia.com
Journal of Pharmaceutical Sciences
|April 12, 2002
Summary
Lyophilization of proteins is improved using a mannitol and sucrose mixture. This formulation enables faster drying at higher temperatures, preventing cake collapse and unstable hydrate formation for stable protein products.
Area of Science:
- Pharmaceutical Sciences
- Biotechnology
- Materials Science
Background:
- Lyophilization (freeze-drying) is crucial for protein stability.
- Traditional formulations face challenges with drying temperatures and cake collapse.
- Excipients like mannitol and sucrose are commonly used but require optimization.
Purpose of the Study:
- To investigate sucrose-mannitol mixtures as excipients for protein lyophilization.
- To optimize lyophilization cycles for enhanced protein cake stability.
- To prevent the formation of unstable mannitol hydrates during secondary drying.
Main Methods:
- Formulation development using specific percentages of sucrose and mannitol.
- Lyophilization cycle optimization, including primary and secondary drying stages.
- Analysis of cake structure (crystalline mannitol, amorphous sucrose) and stability.
Main Results:
- Successful lyophilization of four developmental proteins using a 4% mannitol and 1% sucrose formulation.
- Achieved primary drying at -10°C due to crystalline mannitol, avoiding collapse associated with amorphous sucrose alone.
- Prevented unstable mannitol hydrate formation by conducting secondary drying at ≥40°C.
Conclusions:
- Sucrose-mannitol mixtures provide a robust formulation for protein lyophilization.
- Optimized cycles utilizing these excipients enhance cake stability and drying efficiency.
- This approach offers a viable strategy for stabilizing therapeutic proteins through lyophilization.