The impact of the stopper position and geometry on the freeze-drying cycle of pharmaceutical products

This is the authors' abstract. We don't add key points for this paper.

Glass vials with silicone stoppers are commonly used for pharmaceutical freeze-drying. Vials are partially stoppered before lyophilization to prevent contamination but introduce resistance to vapor flow through a small aperture. A Computational Fluid Dynamics (CFD) analysis using Comsol Multiphysics assessed mass transport resistance with different stopper geometries. Three case studies, representing conventional batch freeze-drying, continuous freeze-drying, and low-fill-volume drug products, were simulated, comparing stopper effects on process variables. While stoppers minimally influenced conventional freeze-drying, they significantly affected low-fill volume formulations. The study emphasizes the impact of stopper positioning on batch heterogeneity, especially when monitoring vials with thermocouples to infer product resistance. Heightened attention is essential in this regard.