The objective of this project is to advance the understanding of the mechanisms for success and failure of excipients as protein stablilizers in solution, during freezing, drying, and reconstitution. Questions to be addressed during the course of the project include: (1) what are the implications of protein surface modification on protein stabilizer interactions and the capacity of such excipients to protect proteins during processing; (2) when and how do surfactants stabilize proteins in solution, and during freezing, drying, and reconstitution; (3) can the solution thermodynamic model developed by Timasheff and co-workers be used to explain the inhibition of protein chemical degradation kinetics by preferentially excluded solutes; and (4) what processes can account for apparent time-dependent degradation processes in samples stored in dried solids at temperatures below formulation glass transition temperatures.
