Effect of Freeze-Dryer Design on Drying Rate of an Amorphous Protein-Formulation Determined with a Gravimetric Technique

Abstract

A freeze-drying balance was used to determine momentary drying-rate, , of a sucrose/BSA formulation contained in a vial with varying shelf packing density, Ø₂. A comparison between two different laboratory-scale freeze-dryers was made. The effects of Ø₂ on differed between the two units, attributed to drying chamber design and its effects on heat transfer. At high Ø₂ the differences are annulled because of the shielding effects of surrounding vials. Parallel effects of Ø₂ were also found on product temperature, T_b, measured in the balance vial. T_b was used to calculate vial heat transfer coefficient, K_v. K_v was strongly reduced with increasing Ø₂, but reached a plateau value at high Ø₂.

Keywords:

• freeze-drying
• lyophilization
• drying rate
• vial heat transfer coefficient

ACKNOWLEDGEMENTS

The authors wish to thank Michael J. Pikal, University of Connecticut, for supporting the microbalance experiments in his FTS Lyostar II freeze-dryer and for valuable discussions during this period.