Experimental investigation on the ice crystal particle size evolution during the freezing stage of binary solution.

The freeze-drying technology has gained a considerable interest recently for its advantages in preserving biopharmaceutics. The size of ice crystals is of utmost importance during the freeze drying process. However, little is known about the dynamic evolution of ice crystal size. To address this, freeze-drying microscope is introduced in this paper to investigate the particle size evolution and morphology variation of ice crystals, and the impacts of process parameters on the dynamic particle size evolution are also studied. The freezing process, including the freezing front propagation, side branching and the growth of crystals, are experimentally observed. The results show that lognormal distribution could better describe the ice crystal size distribution compared with other counterparts. The average size and the standard deviation increase as freezing stage proceeds. In addition, increasing the mass concentration would lead to the decrease of average diameter and standard deviation, and the effects of cooling rate on the average diameter and the standard deviation exhibits different trends when changing the mass concentration. The research could contribute to a deeper understanding of the ice crystal growth mechanism and provide guidance for optimizing the freezing stage of the freeze drying process.