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Quantitative Analysis of Glassy State Relaxation and Ostwald Ripening during Annealing Using Freeze-Drying
Tigran Kharatyan1,2, Srikanth R Gopireddy2, Toru Ogawa3
1Department of Pharmaceutics and Biopharmaceutics, Kiel University, 24118 Kiel, Germany.
Pharmaceutics
|June 24, 2022
Summary
Annealing pharmaceutical solutions during freeze-drying improves cake structure by causing water molecule rearrangement. This study quantifies how annealing affects ice crystal size and phase transitions, revealing distinct kinetics for glassy state relaxation and Ostwald ripening.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Physical Chemistry
Background:
- Supercooling in pharmaceutical solutions during freezing can negatively impact freeze-drying outcomes.
- Annealing (thermal treatment) of frozen solutions can mitigate issues like prolonged drying times and cake collapse.
- Understanding water molecule rearrangement during annealing is crucial for optimizing lyophilization.
Purpose of the Study:
- To demonstrate that annealing induces water molecule rearrangement in frozen binary aqueous solutions.
- To quantify the effects of annealing on ice crystal size and phase volume fractions.
- To compare the distinct kinetic processes of glassy state relaxation and Ostwald ripening.
Main Methods:
- Utilized freeze-drying microscopy and image labeling techniques.
- Analyzed 10% (w/w) sucrose and trehalose solutions.
- Quantified ice crystal sizes and volume fractions of crystalline and amorphous phases post-annealing.
Main Results:
- Annealing led to a decrease in the amorphous phase volume due to vitreous water crystallization (glassy state relaxation).
- The crystalline phase increased in volume through coarsening (Ostwald ripening).
- Both processes were observed to occur simultaneously but exhibit different kinetics.
Conclusions:
- Annealing promotes distinct, simultaneous processes of glassy state relaxation and Ostwald ripening in frozen pharmaceutical solutions.
- This study provides the first quantitative comparison of these two phenomena.
- Findings offer insights into optimizing freeze-drying cycles for improved product stability and quality.
