Effect of temperature ramp rate during the primary drying process on the properties of amorphous-based lyophilized cake, Part 2: Successful lyophilization by adopting a fast ramp rate during primary drying in protein formulations

摘要

In the lyophilization process for injections, the shelf temperature (Ts) and chamber pressure (Pc) have mainly been investigated to optimize the primary drying process. The objective of this study was to show that lyophilization of protein formulations can be achieved by adopting a fast ramp rate of Tsin the beginning of the primary drying process. Bovine serum albumin was used as the model protein, and seven different lyophilized formulations obtained were stored at elevated temperature. We found that although acceptable cake appearance was confirmed by the fast ramp cycle, all formulations of lyophilized cakes obtained by the slow ramp cycle severely collapsed (macrocollapse). It is thought that the collapse in the slow ramp cycle occurred during the shelf ramp in the beginning of primary drying and that insufficient removal of water from the dried matrix caused viscous flow (product collapse). Regarding storage stability, moisture-induced degradation was confirmed in some of the formulations prepared by the slow ramp cycle, whereas all lyophilized BSA formulations prepared by the fast ramp cycle were stable. Thus, the results indicate that the ramp rate appears to be one of the critical operational parameters required to establish a successful lyophilization cycle.