Dielectric characterization of thermodynamic first order events in model frozen systems intended for lyophilization.

The degree and ease with which permanent dipoles in a frozen sample orient in an applied electric field is affected during thermal transitions. This motion can be monitored with dielectric analysis (DEA) at low AC frequencies (< approximately 300,000 Hz). The systems characterized with respect to their behavior in the frozen state consisted of common lyophile excipients in aqueous solutions known to exhibit typical thermodynamic first order transitions. Prior to freezing, solution samples were placed on an interdigitated electrodes and served as the dielectric component of the resulting capacitor. Plots of derivative of dielectric permittivity with respect to time (or temperature) showed the presence of frequency independent peaks (signifying a first order event) at temperatures that coincided with eutectic temperatures (ca. -22 degrees C for sodium chloride-water and ca. -5 degrees C for mannitol-water), amorphous to crystalline transition temperatures (ca. -25 degrees C for mannitol-water), and/or freezing point depression values in water. The values obtained by DEA correlated well with differential scanning calorimetry (DSC) and literature values. DEA appears to offer added insight over established techniques by not only determining the temperature at which these events occur, but also by defining the thermodynamic order of the event.