Experimental and simulation-based investigation of the influence of freezing and annealing on the microstructure in lyophilisates

This work explores the impact of freezing and annealing conditions on the microstructure of lyophilisates, using a combination of experimental techniques, such as freeze-drying microscopy and differential scanning calorimetry, and a theoretical phase-field model. 

The research initially focused on how temperature ramps in freeze-dryers influence the recalescence and crystallisation phases, where the temperature in samples rises during freezing due to an exothermic phase transition. Temperature profiling within vials established a correlation between nucleation temperature and the duration of the recalescence and crystallisation phases. Findings indicated that lower nucleation temperatures reduce the period of elevated temperatures, which is crucial during the initial freezing stage.

Moreover, this study examined the microstructural effects of recalescence and crystallisation using a freeze-drying microscope. In cases without a temperature increase, a fine network of crystalline and amorphous phases was observed, complicating phase differentiation. Conversely, samples subjected to controlled temperature increases mimicking in-vial conditions during recalescence and crystallisation showed distinct, grain-like ice crystals, which are comparable to the pores observed in lyophilisates.

To complement experimental observations, a two-dimensional phase-field model was developed, later expanded to three dimensions, to simulate and predict morphological changes within the lyophilisate during annealing. The simulations not only provided insights into the dynamics of ice crystal growth and the distribution changes during annealing but also examined additional parameter such as the surface area of the matrix phase, as well as the conjunction areas between neighbouring ice crystals.

In conclusion, this work highlights the complex interplay between processing conditions and microstructural outcomes in lyophilisates.
 

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Zitierform:
Kharatyan, T.L., 2024. Experimental and simulation-based investigation of the influence of freezing and annealing on the microstructure in lyophilisates.
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