Pharmaceutical Lyophilization/Freeze Drying

  • Many pharmaceuticals are not stable in aqueous solution for a long time. Freeze-drying, or lyophilizing the material to remove water is one of the final steps of aseptic pharmaceutical production. AMS1300 can reduce processing time by accurately identifying the endpoints of freeze drying. Additionally, AMS1300 can be used to detect contamination and monitor the system for vacuum leaks. The AMS1300 can be easily retrofitted to existing freeze-drying systems due to its ultra-compact footprint that lends itself to space limitation in labs and production plants.
  • The process of lyophilization involves sublimating the water in two phases using thermal control under vacuum. The primary drying endpoint during lyophilization removes frozen water. The secondary drying endpoint, which removes liquid water, requires increasing the temperature. Increasing the temperature prematurely (before passing the primary drying endpoint) can reduce the stability of the final product.
  • Typically, endpoints are monitored using a Pirani pressure gauge, which measures the thermal conductivity of the gas in the lyophilization chamber. When the Pirani gauge pressure signal drops sharply, the gas in the chamber is changing from water vapor to nitrogen, indicating that a drying endpoint has passed.

Why using the AMS Smart SpectrometerTM solution to monitor the lyophilization process

  • The AMS1300 is a fully integrated process control mass spectrometer. It is robust and reliable, due to its miniature quadrupole array design. It operates at high pressure with abundant ions allowing the utilization of a rugged Faraday Cup detector, which gives stable detector sensitivity over the operational time, compared to an Electron Multiplier detector
  • The AMS1300 provides real-time data for process optimization and end-point detection in pharmaceutical lyophilization by directly detecting water vapor. The AMS1300 measurements are more sensitive than the Pirani gauge at determining the secondary drying endpoint allowing operators to shorten runtimes, hence increasing the freeze-drying process efficiency.
  • The AMS1300 is calibrated to detect silicone oil. Silicone oil circulates among the shelves of a freeze-dryer to control temperature. Thermal and pressure cycles, as well as stresses during sample loading and unloading, may cause tiny leaks of Silicone Oil heat transfer fluid to seep into the aseptic freeze-dryer chamber and compromise the valuable pharmaceuticals’ quality.
  • The AMS1300 proprietary Silicone oil filtration system allows the detection of any Si-Oil contamination during the freeze-drying process while protecting the AMS hardware from degradation due to Si-Oil deposition.
  • The AMS1300 monitors for vacuum leaks in the lyo sytem by detecting helium. The AMS1300 detects water vapor, nitrogen, oxygen, helium, and silicone oil with ± 0.3% accuracy, with a limit of detection of 200 ppm for silicon oil and 500 ppm for water.
  • The AMS1300 uses proprietary algorithms for accurate calculations of the mole fractions of each gas component (silicone oil, helium, water vapor, nitrogen, and oxygen).