Freeze Drying of Pharmaceutical Excipients Close to Collapse Temperature: Influence of the Process Conditions on Process Time and Product Quality

The aim of this article is to investigate the characteristics of a vial freeze-dried product as a function of the temperature at which the primary drying is carried out. The effect of the drying temperature and composition on the product appearance and final characteristics (apparent density and rehydratability) of pure substances (mannitol, sucrose, and dextran) has been studied: rehydratability is faster for the product freeze dried at lower temperature, when the structure of the product is more porous and softer; higher rehydration rates were also observed for samples obtained from lower initial concentration. In case of binary mixtures (mannitol and dextran, sucrose and dextran) the rehydratability gets worse when higher drying temperatures are used, whereas the relative composition has a smaller effect. Nevertheless, high drying temperatures are required to shorten the process, both in case of pure substances and in case of binary mixtures; thus, it is important to consider the process time-product quality relationship to choose the optimal drying temperature. Finally, we show that the freeze drying of mixtures can be easier and faster than that of one of the components alone; this is partly a consequence of the higher temperatures allowed, but it is evident that in some cases the drying kinetics can be higher even with the same process temperature.