Changes in the physical state of model mixtures during freezing and drying: Impact on product quality

The factors which govern the effective freeze-drying of pharmaceutical and biotechnological products are reviewed from the viewpoint of product formulation and the thermophysical states that can exist during the process. With the aid of model mixtures of water with sucrose and sodium chloride it is shown how liquid/solid phase changes during the freezing and rewarming of the frozen mixtures can be controlled and monitored by differential scanning calorimetry. The changes can involve the crystallization of water and NaCl . 2H(2)O. It is demonstrated how the conditions under which the crystalline phases are formed and how changes in the thermomechanical properties of the remaining vitreous phase during warming are basic to the optimization of freeze-drying process cycles. (C) 1996 Academic Press, Inc.