Purpose: Measurement of the kinetic development of shrinkage and cracking of an amorphous trehalose cake as they take place during lyophilization.
Methods: A novel technique has been developed which monitors a vial in situ during the freeze-drying cycle. The 2-dimensional degrees of shrinkage and cracking in its top surface are determined quantitatively using a digital camera and evaluated using AxioVision.
Results: Shrinkage and cracking develop largely already during programmed primary drying and are coupled. For trehalose, sucrose and maltose no clear correlation between shrinkage and wg' is found. There is no dependence of cake rim detachment from the vial inner surface on the trehalose concentration. Cake adhesion is therefore likely not the only determining factor for detachment and shrinkage.
Conclusions: If shrinkage can occur during primary drying, then this relaxes the drying tension produced by desorption of non-frozen water out of the amorphous structure left behind as the sublimation front passes through a volume element, and causes little or no cracking. If shrinkage is restrained, then the drying tension is relaxed by cracking of the brittle cake.