Formulation Development In Freeze-Dried Pharmaceuticals

By Adora Padilla

Lyophilization

• Freezing
  • Typically involves cooling product to -40 °C or lower
  • Nucleation of ice and concentration of solute
  • Final concentrations can reach 20 to 50 times initial starting concentrations
  • Annealing –used to increase size of ice crystals in order to decrease drying time and/or to allow for crystallization of bulking agent
• Primary drying
  • Shelf temperature increased and chamber pressure reduced to optimize sublimation of ice without exceeding product collapse temperature
• Secondary drying
  • Removal of unfrozen water at higher temperatures –typically 25 °C to 40 °C