Optimization of the secondary drying step in freeze drying using TDLAS technology

Area of Science:

• Pharmaceutical Science
• Chemical Engineering
• Analytical Chemistry

Background:

• Secondary drying in freeze-drying is often empirical due to a lack of real-time, noninvasive monitoring tools.
• Accurate control of residual moisture is critical for the stability and efficacy of lyophilized products, especially antibody formulations.

Purpose of the Study:

• To apply Tunable Diode Laser Absorption Spectroscopy (TDLAS) for noninvasive monitoring and control of the secondary drying phase in freeze-drying.
• To establish a method for targeting specific intermediate moisture contents in lyophilized products.

Main Methods:

• Utilized bovine serum albumin/sucrose mixtures as a model for concentrated antibody formulations.
• Employed TDLAS to measure water desorption rates noninvasively during secondary drying at various temperatures.
• Validated TDLAS results against Karl Fischer titration for residual moisture content determination.

Main Results:

• Demonstrated a linear relationship between residual moisture and water desorption rate, enabling anchor point evaluation.
• Achieved high accuracy (approx. 0.5%) in mass flow integration from the TDLAS-derived anchor point.
• Successfully monitored and targeted intermediate moisture contents in a confirmation experiment.

Conclusions:

• TDLAS provides an accurate and noninvasive method for monitoring secondary drying in freeze-drying.
• This approach offers significant potential for optimizing sterile pharmaceutical freeze-drying processes on a production scale.