Mechanical Characterization of Vial Strain During Freezing and Thawing Operations Using Amorphous Excipients

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Pharmaceutical vials experience mechanical stresses during freeze-drying.
• Understanding these stresses is crucial for preventing vial breakage and maintaining formulation stability.
• Excipient crystallization is a known risk factor for primary packaging damage.

Purpose of the Study:

• To investigate mechanical stresses and strains on pharmaceutical glass vials during freezing and thawing.
• To correlate strain behavior with formulation properties and temperature transitions.
• To explore the utility of strain measurements in formulation design and process analytical technology.

Main Methods:

• Utilized a custom wireless sensor for in-situ strain measurements within a laboratory-scale freeze-dryer.
• Tested model pharmaceutical formulations (sucrose and trehalose) at various concentrations (5-20% w/v).
• Monitored strain output in relation to temperature, particularly near the glass transition temperature (Tg') and ice melting points.

Main Results:

• Strain measurements peaked near the glass transition temperature (Tg') for formulations between 5-20% w/v.
• Below 5% w/v, strain showed two peaks: one near ice melting and another near Tg'.
• Maximum strain magnitude was observed at concentrations between 4-5% w/v where the two peaks merged.

Conclusions:

• Strain behavior is linked to the transition from elastic to viscoelastic properties of the frozen matrix around Tg'.
• Strain measurements offer insights into formulation behavior and potential mechanical risks.
• Strain data may be valuable for optimizing formulation design and implementing process analytical technology to mitigate stresses.