Determining Maximum Sublimation Rate for a Production Lyophilizer: Computational Modeling and Comparison With Ice Slab Tests

Abstract Equipment capability is an important factor in scale up and technology transfer for lyophilized pharmaceutical products. Experimental determination of equipment capability limits, such as the maximum sublimation rate at a given chamber pressure, is time-intensive for production lyophilizers. Here, we present computational fluid dynamics modeling of equipment capability and compare it with experimental data for minimum controllable pressure ice slab sublimation tests in a 23 m 2 shelf area freeze dryer. It is found that the vapor flow in the production scale is characterized by turbulent effects at high sublimation rates. For the considered freeze dryer configuration, the onset of turbulence occurs at a sublimation rate of 17 kg/h and leads to an increase in the minimum controllable pressure by 3-4 mTorr for the flow rates up to 40 kg/h. Variations in the shelf and duct orientations as well as the valve stroke distance and their effect on the equipment limit and pressure uniformity are also discussed. The minimum controllable pressure measured experimentally agreed within 5% with computational fluid dynamics results. For high vapor sublimation rates at final stages of ice slab testing, the condenser load affects the product chamber pressure control. Estimate of condenser pressure changes because of ice accumulation has been included.