3D mathematical modelling to understand atypical heat transfer observed in vial freeze-drying
Résumé
In pharmaceutical freeze-drying, the position of the product container (vial) on the shelf of the equipment
constitutes a major issue for the final product quality. Vials located at the shelf edges exhibit higher
product temperature than vials located in the centre, which in turn often results in collapsed product. A
physics-based model was developed to represent heat transfer phenomena and to study their variation
with the distance from the periphery of the shelf. Radiation, conduction between solids, and conduction
through low-pressure water vapour were considered. The modelling software package COMSOL
Multiphysics was employed in representing these phenomena for a set of five vials located at the border
of the shelf, close to the metallic guardrail. Model predictions of heat fluxes were validated against experimental
measurements conducted over a broad range of shelf temperatures and chamber pressures representative
for pharmaceutical freeze-drying. Conduction through low-pressure water vapour appeared
as the dominant mechanism explaining the additional heat transfer to border vials compared to central
ones. The developed model constitutes a powerful tool for studying heterogeneity in freeze-drying while
reducing experimental costs.
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