lec22_formulation of biotech products (II)
Freeze-Drying Process
Sublimation vs. Evaporation
Sublimation: Direct transition from solid to gas without passing through the liquid phase.
Evaporation: Transition from liquid to gas.
Application: Freeze drying involves sublimation.
Lyophilization (Freeze Drying)
Notable Product: ASTRONAUT Ice Cream (sample weight: 19g).
Lyophilization Procedure
Initial Freezing:
Objective: Freeze the material at -50°C to -80°C.
Reduction of Pressure:
Surrounding pressure is significantly reduced.
Primary Drying:
Heat provided to facilitate sublimation of frozen water (95% removal).
Duration: Several days.
Secondary Drying:
Low-pressure conditions maintained (in ubar).
Temperature can exceed 0°C to remove tightly bound water.
Final Step: Vacuum is broken using inert gas (e.g., nitrogen).
Target Final Humidity: ~2%.
Equipment Used: Compressor door, heated shelves, refrigeration coils, vacuum pump.
Physical Appearance During Lyophilization
Stages: Liquid freezing, primary drying, secondary drying.
End Product: Lyophilized formulation contains minimal unbound and bound water.
Advantages of Lyophilization
Convenient storage: Can be stored at room temperature as opposed to -80°C.
Ease of shipment.
Reduced degradation of proteins in solid compared to solution.
Cost-effective solid preparation of active protein drugs.
Prolongs shelf-life of protein formulations.
Significant relevance: 46% of FDA-approved biologic products are freeze-dried.
Considerations in Lyophilization
Protein must retain native state.
Minimize protein unfolding.
Maintain low residual moisture (<2%).
Optimize formulation to prevent chemical degradation.
Routes of Protein Drug Delivery
Main Routes
Subcutaneous (S.C.)
Intravenous (I.V.)
Oral and pulmonary routes have limited effectiveness.
Why Not Oral Route?
Ineffectiveness: Liquid proteins are apt to degrade in the GI tract.
Human Digestive Mechanism:
Efficient at breaking down dietary proteins into amino acids.
Enzymatic breakdown occurs through various peptides in the GI tract.
Challenges: High molecular weight of intact protein drugs makes absorption difficult.
Sterilization of Biotech Products
Requirement: Essential for parenteral formulations.
Common Methods:
Heat
Radiation
Filtration (preferred, especially membrane filtration at 0.22 μm).
Assembly of protein formulations must occur under aseptic conditions due to protein sensitivity.
lec22_formulation of biotech products (II)
Freeze-Drying Process
Sublimation vs. Evaporation
Sublimation: Direct transition from solid to gas without passing through the liquid phase.
Evaporation: Transition from liquid to gas.
Application: Freeze drying involves sublimation.
Lyophilization (Freeze Drying)
Notable Product: ASTRONAUT Ice Cream (sample weight: 19g).
Lyophilization Procedure
Initial Freezing:
Objective: Freeze the material at -50°C to -80°C.
Reduction of Pressure:
Surrounding pressure is significantly reduced.
Primary Drying:
Heat provided to facilitate sublimation of frozen water (95% removal).
Duration: Several days.
Secondary Drying:
Low-pressure conditions maintained (in ubar).
Temperature can exceed 0°C to remove tightly bound water.
Final Step: Vacuum is broken using inert gas (e.g., nitrogen).
Target Final Humidity: ~2%.
Equipment Used: Compressor door, heated shelves, refrigeration coils, vacuum pump.
Physical Appearance During Lyophilization
Stages: Liquid freezing, primary drying, secondary drying.
End Product: Lyophilized formulation contains minimal unbound and bound water.
Advantages of Lyophilization
Convenient storage: Can be stored at room temperature as opposed to -80°C.
Ease of shipment.
Reduced degradation of proteins in solid compared to solution.
Cost-effective solid preparation of active protein drugs.
Prolongs shelf-life of protein formulations.
Significant relevance: 46% of FDA-approved biologic products are freeze-dried.
Considerations in Lyophilization
Protein must retain native state.
Minimize protein unfolding.
Maintain low residual moisture (<2%).
Optimize formulation to prevent chemical degradation.
Routes of Protein Drug Delivery
Main Routes
Subcutaneous (S.C.)
Intravenous (I.V.)
Oral and pulmonary routes have limited effectiveness.
Why Not Oral Route?
Ineffectiveness: Liquid proteins are apt to degrade in the GI tract.
Human Digestive Mechanism:
Efficient at breaking down dietary proteins into amino acids.
Enzymatic breakdown occurs through various peptides in the GI tract.
Challenges: High molecular weight of intact protein drugs makes absorption difficult.
Sterilization of Biotech Products
Requirement: Essential for parenteral formulations.
Common Methods:
Heat
Radiation
Filtration (preferred, especially membrane filtration at 0.22 μm).
Assembly of protein formulations must occur under aseptic conditions due to protein sensitivity.
