Freeze drying is a dehydration technique commonly used in food processing as well as biological, pharmaceutical and biomedical applications. In these technical scenarios, the application of heat for evaporative drying will either degrade the material to be dried or change its form and structure (Zhang et al., 2018). Freeze drying — also called lyophilization or cryodesiccation — was developed in the early 1940s as a response to these challenges. The technique was instrumental to the survival of Allied Forces’ soldiers injured on the warfront during World War II. Blood plasma and penicillin were preserved with freeze drying and transported to Europe for medical and rehabilitative purposes.

Freeze drying exploits the physical properties of the component it seeks to remove: water. Water is a liquid at atmospheric pressure if its temperature is above 32°F (0°C) and below 212°F (100°C). With an increase in temperature (above 32°F) and a simultaneous drop in pressure (below 0.06 Atm), water transitions to the vapor phase. With a variation of pressure and temperature, water also can change from a solid ice state to vapor without thawing into the liquid state (Cheng et al, 2014). This is known as sublimation.

A typical freeze-drying process is designed based on this well-understood behavior. It utilizes three steps:

  • Freezing.
  • Sublimation.
  • Adsorption.

In the freezing phase, the temperature of the material to be dried is reduced in a chilling/refrigerated compartment. (Typically, the temperature is reduced below the triple point of water.)

This sets the stage for the sublimation phase, which is also known as primary drying. This phase involves pressure reduction (below 0.006 Atm) and the addition of heat to increase the material’s temperature. The phase typically is achieved through indirect heating with a heat transfer fluid. It causes ice-water crystals to sublime directly into the vapor phase, thereby removing up to 95 percent of the water content of the material.

mineral-oil-based fluid

One dual-zone mineral-oil-based fluid has a minimum temperature of -26°F (-32°F) and a maximum bulk temperature of 601°F (316°C). This fluid covers the typical process temperature spectrum in freeze-drying applications.

In the last phase, adsorption (also known as secondary drying) removes most of the remaining water content. By increasing the temperature above the primary drying level and maintaining a vacuum in the drying chamber, electrovalent bonds between water molecules and the material are broken, liberating the former into the gas phase. Again, the increase in temperature in the final phase is achieved using a heat transfer fluid.

The process description highlights the importance of heat transfer fluids used for precise temperature control in the freeze-drying process. Many equipment manufacturers and equipment engineers only specify silicone oil as their heat transfer fluid of choice. The physical properties of silicone oil heat transfer fluid cover the broad spectrum that is required for freeze drying. There is a misconception in the industrial circles, however, that the freeze-drying process forbids other types of heat transfer fluids. This article suggests alternatives that offer significant technical and commercial benefits to end users.

Low temperature, mineral-oil-based heat transfer fluids have been used successfully in freeze drying and are viable alternatives to silicone oil. These fluids meet the technical specifications of the freeze-drying process. They possess adequate thermal capacity and include additives that mitigate oxidation. For instance, a currently available dual-zone, mineral-oil-based fluid has a minimum temperature of -26°F (-32°F) and a maximum bulk temperature of 601°F (316°C). This fluid covers the typical process temperature spectrum in freeze-drying applications. It also has a heat capacity approximately 10 percent higher than silicone oil. This is in addition to the fact that mineral-oil-based fluids are nontoxic, nonhazardous and can be disposed of safely.

Low temperature mineral-oil

Low temperature mineral-oil and glycol heat transfer media have physico-chemical properties that demonstrate a good fit for freeze-drying applications.

For ultra-low temperature freezing scenarios, silicone oil has cryogenic limitations. It cannot be used beyond its minimum operating temperature of -63°F (-53°C). In contrast, ultra-low temperature mineral-oil formulations can be used for precise temperature control in applications with temperature specifications ranging from -120°F up to 150°F (-84°C up to 65°C).

In the era of budget cuts, end users continually seek opportunities to optimize their operational costs. It is logical to assume that a worthwhile consideration for an alternative heat transfer medium for use in lyophilization machines should not only be beneficial from a technical perspective but also from a commercial standpoint. Freeze drying is the most expensive unit operation in the production of lyophilized products (Yalkowsky & Patel, 1991). Mineral oils can offer cost savings when compared to silicone oil; hence, manufacturing companies can reduce the operational expense on heat transfer fluids.

Glycols also hold promise for freeze drying based on some of the parameters already mentioned. In a 2014 analysis of heat transfer mechanism for shelf vacuum freeze drying conducted by Cheng et al. (2014), a 50 percent ethylene glycol solution was successfully utilized as a heat transfer fluid in a freeze-drying application. Rosa et al. (2016) used a 96 percent v/v ethanol in their freeze-drying equipment. Considering the food and drug safety requirements, propylene glycol is a more appropriate option in pharmaceutical and food processing applications. Its relatively low cost, low pour point and low viscosity make it suitable for shelve heating in freeze drying.

heat transfer fluid

Several criteria should be considered when choosing a heat transfer fluid for an industrial application, including design constraints, plant limitations and process objectives.

In conclusion, in this article, a case for alternative approaches to material heating in freeze drying is made. Low temperature mineral oils and glycols are cost-effective heat transfer media with physico-chemical properties that demonstrate a good fit. Original equipment manufacturers and maintenance managers are provided with technically viable alternates for initial factory fill and fluid replacements, respectively. It should be noted that due to the dissimilarity of chemistries, a top off of existing silicone oil with a mineral-oil-based heat transfer fluid or glycol is discouraged. The heat transfer equipment should be drained of the existing fluid before a charge of virgin heat transfer fluid is introduced into the heat transfer loop.

Ultimately, several criteria should be considered when choosing a heat transfer fluid for any industrial application. With the multiplicity of design constraints, plant limitations and process objectives, it is always advisable to consult a heat transfer fluid specialist to discuss an optimal selection. PC


References

Cheng, C.-C., Tsai, S.-M., Cheng, H.-P., & Chen, C.-H. “Analysis for heat transfer enhancement of helical and electrical heating tube heat exchangers in vacuum freeze-drying plant.” International Communications in Heat and Mass Transfer, 58 (2014), p. 111-117.

Hong-Ping Cheng H., Shian-Min Tsai S., and Chin-Chi Cheng C. “Analysis of Heat Transfer Mechanism for Shelf Vacuum Freeze-Drying Equipment,” Advances in Materials Science and Engineering, Vol. 2014, Article ID 515180. https://doi.org/10.1155/2014/515180.

Rosa, M., Tiago, J. M., Singh, S. K., Geraldes, V., & Rodrigues, M. A. (2016). “Improving Heat Transfer at the Bottom of Vials for Consistent Freeze Drying with Unidirectional Structured Ice.” AAPS Pharmscitech. Vol. 17(5), p. 1049-1059.

Yalkowsky, S. H., & Patel, S. D. (n.d.). “Acceleration of Heat Transfer in Vial Freeze-Drying of Pharmaceuticals. II. A Fluid Cushion Device.” Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists. Vol. 9(6), p. 753-758.

Zhang, S., Luo, J., Wang, Q., & Chen, G. (2018). “Step utilization of energy with ejector in a heat driven freeze drying system.” Energy. Vol. 164, p. 734-744.