Sublimation Kinetics during Freeze-Drying of Pharmaceutical Protein Formulation

Abstract

The influence of total gas pressure and shelf temperature on sublimation kinetics of BSA-based formulation in glass vial as geometrical configuration was determined with a pilot freeze-dryer in standard operating freeze-drying conditions.

The sublimation rate curves showed three different periods with a plateau corresponding to a stationary regime. These kinetics data were mainly dependent on the shelf temperature and slightly influenced by the total gas pressure. Thus, the sublimation process in our conditions was mainly governed by overall heat transfer rate from the plate and from the surroundings to the sublimation front.

Moreover, it proved that the water vapor mass transfer mechanism through the dried layer occurs by molecular diffusion in Knudsen regime.

Finally, these experimental sublimation kinetics data were found in a quite fair agreement with the set up results. They confirm the validation of previous modeling of mean product temperature profiles during the freeze-drying by using the finite element code FEMLAB in real vial geometry (2-D).

Keywords:

• Freeze-drying
• Heat and mass transfer
• Pharmaceutics
• Sublimation kinetics

ACKNOWLEDGEMENT

This work was supported by a grant from European community (GROWTH Project GRD1-2001–40259-RTD).