GOALI: Modeling and Control of Fluid Dynamics and Ice Formation in Pharmaceutical Freeze-Drying

Purdue University, West Lafayette IN

Investigators

Abstract

0829047 Alexeenko Freeze-drying is widely used in pharmaceutical manufacturing to extend the shelf life of medical drugs and to provide easy shipping and storage. The goal of freeze-drying is to remove the solvent in such a way that the sensitive molecular structure of the active substance of a drug is least disturbed, and to provide a sterile powder that is quickly and completely rehydrated upon the addition of water. This is done by fast freezing followed by sublimation. Freeze-drying is both a time- and energy-intensive manufacturing process. For example, freeze-drying of 50 milliliters of an experimental protein drug takes up to three days and more than 2,000,000 BTU of energy. Currently, the design of freeze-drying equipment, both laboratory-scale and industrial, is based largely on empirical knowledge. The PIs will apply numerical simulations of vapor and non-condensable gas transport in a freeze-dryer chamber and develop models of vapor/ice interphase transport in a condenser. These large-scale simulations will model vapor and noncondensable gas flow and ice formation in freeze-drying using computational fluid dynamics and the direct simulation Monte Carlo method. Numerical modeling will provide insight into the control of the biopharmaceutical freeze-drying process and the design of compact condensers. Experimental studies will validate the developed models by comparison position dependence of sublimation rates in a freeze-dryer chamber under controlled radiative and conductive heat transfer conditions; water vapor flow rates in the chamber-condenser connector by tunable diode laser absorption spectroscopy; ice formation rates and geometric shapes in the condenser for various condensing surface configurations and temperatures; and a wide range of chamber-to-condenser pressure ratios. The validated models and simulation approaches will form a knowledge base by which future designs of freeze-drying systems and processes will be guided in a physics-based as opposed to an empirical approach. Understanding the fluid dynamics of the water vapor and non-condensable gas as well as the dynamics of vapor/ice interface in freeze-dryers will accelerate the development of freeze-dried products and decrease drug manufacturing costs, which will have a very high societal impact.