Cake shrinkage during freeze drying: a combined experimental and theoretical study

Area of Science:

• Pharmaceutical Sciences
• Chemical Engineering
• Materials Science

Background:

• Cake shrinkage is a critical issue in lyophilization (freeze-drying), impacting product quality and stability.
• Understanding the influence of process parameters on shrinkage is essential for optimizing freeze-drying cycles.

Purpose of the Study:

• To investigate cake shrinkage during lyophilization using experimental and theoretical approaches.
• To determine the effect of shelf temperature during primary and secondary drying on cake shrinkage.

Main Methods:

• Freeze-drying experiments with 5% sucrose solutions, altering drying protocols to vary product temperature.
• Manometric Temperature Measurement (MTM) for resistance data and Passage Freeze-Drying software for theoretical simulation.
• Quantification of shrinkage using Brunauer, Emmeth, Teller (BET) Specific Surface Area (SSA) analysis and mercury porosimetry.

Main Results:

• Approximately 17% cake shrinkage occurred even at temperatures well below the glass transition temperature (Tg).
• Lower shelf temperatures during primary drying and slower ramp rates during secondary drying increased SSA.
• Process and product temperature variations accounted for only an additional 2%-3% shrinkage.

Conclusions:

• Cake shrinkage during lyophilization of sucrose is primarily an intrinsic property, with significant shrinkage (~17%) occurring regardless of drying conditions.
• Secondary drying conditions impact shrinkage, but are a second-order effect; maintaining product temperature below Tg is crucial.
• Optimizing shelf temperature and ramp rates can slightly modulate shrinkage but do not eliminate the inherent phenomenon.