Freeze drying, also known as lyophilization, is a low-temperature dehydration process that includes turning a solid into a gas without turning it into a liquid. It is the leading drying methodology used for nano-derived and biopharmaceutical therapeutics. Three processes make up the process: freezing, primary drying (ice sublimation), and secondary drying (unfrozen water desorption). During freezing the solutes crystalize to form eutectic ice. The ice crystals evaporate during primary drying when the pressure is lowered below the triple point of water and heat is applied to produce the latent heat of sublimation. By means of molecular diffusion through the glassy frozen matrix, secondary drying starts to extract any remaining water from the frozen amorphous particles that have formed. Pressure is crucial in freeze drying and is employed between 1 mbar (−20 °C) and 0.03 mbar (−50 °C to −60 °C). By 2024, the worldwide lyophilization market is expected to be worth US$1.14 billion, and by 2034, it is expected to grow to US$2.61 billion. About 50% of the biopharmaceuticals available in the market are lyophilized. The lyophilized parenteral drugs are Remdesivir, Docetaxel, and Doxorubicin and the lyophilized oral disintegrating tablets are Terbutaline sulphate, Deferasirox, and Rosuvastatin which showed enhanced bioavailability. Freeze drying enhances the shelf-life, bioavailability and pharmacokinetic parameters of biopharmaceuticals (enzymes, peptides, oligonucleotides, monoclonal antibodies, DNA preparations, vaccines, antibody-drug conjugates, therapeutic proteins), and mAB (monospecific antibodies). The effect of active pharmaceutical ingredient (API), formulation components, primary drying conditions, scale-up, and technical transfer are the challenges in lyophilization.

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Freeze Drying of Pharmaceutical Products for Injectable and Oral Use

  • Ashwani,
  • Reetu Garg,
  • G. Baba Shankar Rao,
  • Dalapathi Gugulothu

摘要

Freeze drying, also known as lyophilization, is a low-temperature dehydration process that includes turning a solid into a gas without turning it into a liquid. It is the leading drying methodology used for nano-derived and biopharmaceutical therapeutics. Three processes make up the process: freezing, primary drying (ice sublimation), and secondary drying (unfrozen water desorption). During freezing the solutes crystalize to form eutectic ice. The ice crystals evaporate during primary drying when the pressure is lowered below the triple point of water and heat is applied to produce the latent heat of sublimation. By means of molecular diffusion through the glassy frozen matrix, secondary drying starts to extract any remaining water from the frozen amorphous particles that have formed. Pressure is crucial in freeze drying and is employed between 1 mbar (−20 °C) and 0.03 mbar (−50 °C to −60 °C). By 2024, the worldwide lyophilization market is expected to be worth US$1.14 billion, and by 2034, it is expected to grow to US$2.61 billion. About 50% of the biopharmaceuticals available in the market are lyophilized. The lyophilized parenteral drugs are Remdesivir, Docetaxel, and Doxorubicin and the lyophilized oral disintegrating tablets are Terbutaline sulphate, Deferasirox, and Rosuvastatin which showed enhanced bioavailability. Freeze drying enhances the shelf-life, bioavailability and pharmacokinetic parameters of biopharmaceuticals (enzymes, peptides, oligonucleotides, monoclonal antibodies, DNA preparations, vaccines, antibody-drug conjugates, therapeutic proteins), and mAB (monospecific antibodies). The effect of active pharmaceutical ingredient (API), formulation components, primary drying conditions, scale-up, and technical transfer are the challenges in lyophilization.