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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

  1. Initial Freezing:

    • Objective: Freeze the material at -50°C to -80°C.

  2. Reduction of Pressure:

    • Surrounding pressure is significantly reduced.

  3. Primary Drying:

    • Heat provided to facilitate sublimation of frozen water (95% removal).

    • Duration: Several days.

  4. 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.

CT

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

  1. Initial Freezing:

    • Objective: Freeze the material at -50°C to -80°C.

  2. Reduction of Pressure:

    • Surrounding pressure is significantly reduced.

  3. Primary Drying:

    • Heat provided to facilitate sublimation of frozen water (95% removal).

    • Duration: Several days.

  4. 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.

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