Abstract
The purpose of this study was to examine use of freeze-drying microscopy (FDM) analysis to obtain maximum allowable product temperature during primary drying segment of pharmaceutical lyophilization process. FDM analysis of frozen solutions containing non-crystalline lyoprotectants (trehalose, sucrose, PVP 29,000) showed beginning of physical collapse at temperatures (T_c) several degrees higher than their glass transition temperature of maximally freeze-concentrated solutes (T_g') obtained by thermal analysis. The T_c and T_g' depended on the solute concentration, scanning rate, and cell pressure during the analysis. Loss of the cake structure upon lyophilization of the solutions at the primary drying shelf temperatures above their T_cs indicated relevance of the FDM analysis for the process development.
