Prediction of lyophile collapse temperature by dielectric analysis.

A new method for predicting lyophile collapse temperatures based upon dielectric analysis (DEA) of frozen two component systems is presented. The method, called the take off frequency model (TOF), relies both on the inherent ability of DEA to detect molecular motion and on the abrupt change in viscosity experienced by a frozen sample undergoing a glass-liquid transition. Collapse temperatures for binary glass forming systems (an antibiotic, sucrose, trehalose, or sorbitol, with water) were in good agreement with the values reported in the literature. DEA was easily able to detect glass transitions poorly defined by differential scanning calorimetry (DSC). Conservative lyophilization cycles for simple systems can be quickly determined on the basis of the TOF model.