Observation and Implications of Sonic Water Vapor Flow During Freeze-Drying

Observation and Implications of Sonic Water Vapor Flow During Freeze-Drying
March/April 2004
Jim Searles, Ph.D.
Eli Lilly and Company Global Parenteral Products Commercialization Technology Center Manufacturing Science and Technology
APR
Introduction
Freeze-drying, or lyophilization, is used for a wide range of pharmaceutical products including peptides, proteins, and complex synthetic organic molecules. It is a standard method for stabilizing labile products with limited shelf lives in dilute solution. The objective of lyophilization process development is to deliver a cycle that achieves the following:
Acceptable product quality, consistent within a batch and from batch to batch
Operation within the capabilities of the equipment with appropriate safety margins to ensure robustness
Efficient plant utilization via the shortest possible cycle time and full loading of the lyophilizer
This paper is motivated by the second and third of these objectives: we should design lyophilization cycles so that the drying rate is as high as possible with the freeze-dryer fully loaded with vials, while remaining safely within the capabilities of the equipment.
During freeze-drying the water vapor is driven from the product vials into the product chamber, and from there it travels to the condenser where it condenses upon low-temperature coils. The condenser and product chambers are connected by a cylindrical connecting tube, or duct (see Figure 1). This paper is concerned with the flow of water vapor from the product chamber to the condenser through such a duct. We show data from production runs in which the vapor flow was high enough to "choke" the system, explain the principles behind choked flow, show mathematical modeling results, and detail how freeze dryers can be tested to learn the maximum drying rate they can support.
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