Increasing Lyophilization Productivity, Flexibility, and Reliability Using Liquid Nitrogen Refrigeration–Part 2 - - BioPharm International


Increasing Lyophilization Productivity, Flexibility, and Reliability Using Liquid Nitrogen Refrigeration–Part 2

BioPharm International
Volume 20, Issue 12


This section describes cryogenic heat exchange technologies in terms of freezing characteristics, efficiency of refrigeration utilization, and operating parameters as related to system design. Additional critical design considerations are also outlined.

Refrigeration Utilization Efficiency of Cryogenic Systems

At a given operating temperature and pressure, the fundamental thermophysical properties of cryogenic nitrogen (discussed earlier) make a certain amount of refrigeration available from the fluid. If a 100% efficient cryogenic refrigeration system existed, thermodynamics would still limit the amount of refrigeration available. The design and implementation of the cryogenic cooling system determines what percentage of the available refrigeration is actually recovered by first vaporizing the LN2, and subsequently warming the GN2. The majority of current designs recover most of the latent heat of vaporization. However, designs vary in their capability of recovering the sensible heat by warming the gas. The closer the approach temperature of the gas exhaust is to the heat transfer fluid (HTF) outlet temperature, the higher the efficiency of the cryogenic heat exchanger. We have demonstrated a design that recovers 95–98% of the available refrigeration in a single cryogenic heat exchanger. These efficiencies have been achieved in commercial systems with refrigeration capacities up to 150 kW and operating temperatures as low as –80 C.

Freezing Characteristics

When cryogens are used to cool anything, freezing the entire heat exchange system is a serious concern. LN2 boils at –195.8 C at atmospheric pressure. As discussed earlier, almost all HTFs used in lyophilization freeze at well above this temperature. Freezing of the HTF has limited the widespread application of cryogenic heat exchangers. Some cryogenic heat exchanger designs freeze after only a few hours of operation.2 For longer cooling cycles, several such units are needed to enable parallel defrosting of the frozen heat exchangers and to compensate for refrigeration capacity losses due to the insulating properties of ice.

Recent years have seen the development of nonfreezing cryogenic heat exchanger designs that eliminate the need to switch between frozen and defrosted units. Such nonfreezing designs enable cooling over the long cycles used by lyophilization. They include both a single heat-exchanger design3 and multi-heat-exchanger systems, which use high-pressure fluid ejectors4 or plate-and-frame designs.5 These designs avoid any heat transfer surfaces where HTF is on one side and boiling LN2 on the other by first boiling the LN2 against GN2, and then using only the GN2 to cool the HTF. Consequently, the HTF exchanges heat with only nitrogen gas, thus avoiding the extremely low temperatures of LN2. The nonfreezing single heat exchanger incorporates this capability into one special heat exchanger unit using a proprietary design.3 Nonfreezing multi heat-exchanger systems need multiple heat exchangers, and in some cases an ejector, to accomplish the same result.4,5

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