Freeze-drying microscopy (FDM)

Freeze-drying microscopy (FDM) is a highly valuable technique for studying the behavior of a formulation during freeze-drying and for determining critical product temperatures.

FDM works somewhat like a miniature freeze-dryer. The sample is frozen inside a small microscope chamber by using liquid nitrogen. While applying a vacuum, the temperature is gradually increased and the sample dries. During this temperature ramp, the sublimation front is observed and recorded through a microscope. Changes in the dried layer can be used to determine the state of the system (amorphous or crystalline) and the collapse temperature of the sample.

FDM is mainly employed during lyophilization process development and formulation development, where it is combined with differential scanning calorimetry (DSC) to determine optimal freeze-drying conditions.