Freeze Drying of Pharmaceuticals. On the Change in the Macroscopic Appearance during Freezing and the Critical Temperature necessary for Freeze Drying

Abstract

The low temperature behavior of solutions of simple substances and pharmaceuticals was studied. The authors found noticeable changes in the macroscopic appearance of solutions during freezing of some substances which exhibited the eutectic behavior. Appearance changes were classified into four types: I) no change, II) slight increase in opacity, III) very noticeable formation of clear white spots due to eutectic crystallization with very slow rate of growth of spots, and IV) formation of spots with high rate of growth. The eutectic temperatures (Te) were obtained from the temperature at which spots faded or disappeared. The collapsing temperatures (Tc) were also obtained from the observation during freeze drying, of the temperatures above which the frozen layer of the solution became puffed or collapsed. The electrical resistances of the specimens were measured during cooling and rewarming. These data were compared with each other to discuss the meaning of the changes in appearance during freezing and drying as follows. The formation of spots was due to crowds of eutectic crystal structures. Tcwas observed at Tefor the substances which exhibited the eutectic behavior, and Tcfor the substances which froze solid but in supercooled or super-eutectic states was supposed to be the temperature above which the frozen solution lost solidity. © 1970, The Pharmaceutical Society of Japan. All rights reserved.