Reduction of primary freeze-drying time by electric field induced ice nucleus formation

The potential of a high electric field was utilized to induce ice nucleus formation in aqueous solutions. Using this technique it was possible to reduce the primary drying time during lyophilization. Samples of 10% (w/v) hydroxyethylstarch (HES) solution were frozen at a constant rate of −1 K/min, while nucleation was initiated at temperatures of −1.5, −4.5 and −8.5°C. In contrast, spontaneous nucleation was observed in a range between −11.5 and −17.1°C. Electrically induced nucleus formation has proved to be a reliable method to start crystallization at a desired temperature. Continuous measurement of the weight allowed to determine the drying rate and to detect at which time primary drying was completed. The drying time and the drying rate were found to be strongly dependent on the nucleation temperature during freezing. A relation between the nucleation temperature, the structure of the frozen samples and the drying times could be established.