(696e) Equipment Capability Curves for Large-Scale Freeze-Dryers Based on CFD Analysis

Equipment capability curves are important for designing freeze-dryers and are crucial for process design and scale-up. The capability curve describes the limit beyond which the geometry of the freeze dryer cannot support the flow of the sublimation stream from the drying chamber to the condenser. At the capability limit, the flow is thus choked by the geometry of the freeze dryer. The pressure in the drying chamber then increases and the sublimation rate decreases, which can lead to an increase in product temperature and a possible collapse of the porous cake to a dense plug.

In this study, equipment capability curves for three industrial-sized freeze dryers were derived from computational fluid dynamics (CFD) simulations. In the CFD model, the flow was modeled using a single-component, compressible, single-phase vapor in the laminar flow regime. Condensation on the condenser coils was models via additional desublimation sinks, and the influence of the condenser geometry on the capability curve was evaluated. The capability points defining the capability curve were calculated by setting a very low condenser pressure, a high temperature on the shelves in the chamber and different sublimate mass flows from shelves mimicking the ice slab test. The points of the capability curve are obtained by increasing the mass flow rate of the sublimate until the Mach number reaches 1 (point of choked flow). The pressure in the drying chamber is recorded and represents the result of the simulation, which defines the capability limit point at a certain mass flow rate of the sublimate.

Three lyophilizers were analyzed: two with side-mounted condensers and one with a bottom-integrated condenser. The simulation results are in good agreement with experimental results. This research thus contributes to the understanding, optimization and scale-up of freeze-drying processes using CFD and to the improvement of product quality and process efficiency in pharmaceutical applications.