Non-invasive product temperature determination during primary drying using tunable diode laser absorption...

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Analytical Chemistry

Background:

• Accurate monitoring of product temperature during primary drying is critical for freeze-drying optimization.
• Traditional methods for temperature determination can be invasive or provide limited spatial information.

Purpose of the Study:

• To demonstrate Tunable Diode Laser Absorption Spectroscopy (TDLAS) as a non-invasive technique for determining average product temperature during primary drying.
• To evaluate the application of TDLAS for measuring water vapor concentration and flow velocity to assess sublimation rates and heat transfer coefficients.

Main Methods:

• Utilized TDLAS to continuously measure water vapor concentration and flow velocity in freeze-dryer spool.
• Calculated average sublimation rates and integrated them to determine water removal.
• Determined position-dependent vial heat transfer coefficients (K(v)) using TDLAS data for pure water sublimation.
• Applied weighted K(v) to predict average product temperature in freeze-drying runs with sucrose, mannitol, and glycine solutions.

Main Results:

• TDLAS-derived K(v) data showed good agreement with traditional gravimetric methods.
• Edge vials exhibited 20-30% higher K(v) compared to center vials.
• Predicted TDLAS product temperatures closely matched thermocouple data (within 1-2°C) for various solutions and loading conditions.

Conclusions:

• TDLAS provides a reliable, non-invasive method for monitoring product temperature and sublimation dynamics during freeze-drying.
• The technique enables accurate assessment of heat transfer variations within the freeze-dryer.
• TDLAS is a valuable tool for optimizing freeze-drying cycles and ensuring product quality in pharmaceutical manufacturing.