Kinetics of a phase transition in a frozen solution

The increased use of lyophilization in the preservation of biologicals, foods, and pharmaceuticals has revealed problems of discoloration, meltback, puffing, and collapse, which can result in unacceptable products. Literature reports suggest that some of these problems are related to phase transitions occurring in the frozen solutions. This paper describes the crystallization of mannitol and cefazolin sodium in frozen solution. Data were collected using calorimetric methods in both an isothermal and non-isothermal mode. Analysis of cefazolin sodium data, using the Johnson-Mehl-Avrami equation, indicated that there was a mechanism of heterogeneous nucleation of a two dimensional growth habit. Mannitol data indicated that the controlling crystallization mechanism was not constant over the temperature range studied.