title: Freeze-drying simulation framework coupling product attributes and equipment capability: toward accelerating process by equipment modifications.
abstract: A physics-based model for the sublimation-transport-condensation processes occurring in pharmaceutical freeze-drying by coupling product attributes and equipment capabilities into a unified simulation framework is presented. The system-level model is used to determine the effect of operating conditions such as shelf temperature, chamber pressure, and the load size on occurrence of choking for a production-scale dryer. Several data sets corresponding to production-scale runs with a load from 120 to 485 L have been compared with simulations. A subset of data is used for calibration, whereas another data set corresponding to a load of 150 L is used for model validation. The model predictions for both the onset and extent of choking as well as for the measured product temperature agree well with the production-scale measurements. Additionally, we study the effect of resistance to vapor transport presented by the duct with a valve and a baffle in the production-scale freeze-dryer. Computation Fluid Dynamics (CFD) techniques augmented with a system-level unsteady heat and mass transfer model allow to predict dynamic process conditions taking into consideration specific dryer design. CFD modeling of flow structure in the duct presented here for a production-scale freeze-dryer quantifies the benefit of reducing the obstruction to the flow through several design modifications. It is found that the use of a combined valve-baffle system can increase vapor flow rate by a factor of 2.2. Moreover, minor design changes such as moving the baffle downstream by about 10 cm can increase the flow rate by 54%. The proposed design changes can increase drying rates, improve efficiency, and reduce cycle times due to fewer obstructions in the vapor flow path. The comprehensive simulation framework combining the system-level model and the detailed CFD computations can provide a process analytical tool for more efficient and robust freeze-drying of bio-pharmaceuticals.
authors.affiliation: School of Aeronautics and Astronautics, Purdue University, West Lafayette, IN, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Ganguly
authors.forename: Alina A
authors.initials: AA
authors.lastname: Alexeenko
authors.forename: Steven G
authors.initials: SG
authors.lastname: Schultz
authors.forename: Sherry G
authors.initials: SG
authors.lastname: Kim
mesh_terms: D002138:Calibration; D003198:Computer Simulation; D005612:Freeze Drying / Q000295:instrumentation* / Q000379:methods*; D006358:Hot Temperature; D008956:Models, Chemical; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*; D013696:Temperature
keywords: Baffle; Computational fluid dynamics; Freeze-drying; Process modeling; Valve; Water vapor