ABSTRACT
As the number of biomolecules for potential therapeutic use is increasing, the need to understand their structural complexities and stabilization is also increasing. The lyophilization process still remains as one of the most preferred stabilization methods relative to other drying technologies for the simple reason that it is a low-temperature process and allows processing of biological solutions that are otherwise susceptible to damage (Pikal 2002; Franks 1990). However, lyophilization is a complex process and can cause in-process and storage instabilities if it is not properly designed. The lyophilization process consists of three phases: (1) freezing, (2) primary drying, and (3) secondary drying. The freezing phase involves the conversion of water into solid ice by exposing the solution to temperatures ≤–40°C, followed by primary drying where sublimation of ice is carried out with the application of heat and vacuum. At the end of primary drying, depending on the composition of the formulation, there will still be a significant amount of water left that will be desorbed using elevated temperatures during the secondary drying phase.
