Saving lives, powering rockets, making snacks: The rocket science of freeze-drying

The longer answer involves fluid dynamics, the fusion of interdisciplinary science, serendipity and Purdue innovation.

Alexeenko, a professor of aeronautics and astronautics and chemical engineering and a co-director of Purdue’s William D. Young Institute for Advanced Manufacturing of Pharmaceuticals, began her career working on the intricacies of the way rocket engines work at high altitudes and on sensors that measure fluid behavior on a nanoscale. How that happens works differently when the engines are in the vacuum of space rather than on a planet with gravity and atmosphere. And that, in a way, is how she got involved in the technology of pharmaceutical freeze-drying, called lyophilization.

“I got an email about software I had developed as a grad student,” Alexeenko said. “An engineer asked me a very specific question about it, about calculating the viscosity of nitrogen and water vapor mixture under very strange conditions. I responded and helped him, but then I was curious and asked what he was working on. And it turned out he was working on lyophilization equipment.”

Lyophilization safely and gently removes water from substances while subjecting them to spacelike vacuum, leaving them shelf-stable and easy to reconstitute. Scientists developed the technique at a mass scale during World War II to preserve blood products and penicillin. Today, the process allows drugs and vaccines to be stable and viable for a much longer time and allows them to be shipped long distances without elaborate equipment such as freezers or refrigerators.

“In some ways, lyophilization is very similar to the dynamics of space – to high-altitude aerodynamics,” Alexeenko said. “Of course, some application objectives and requirements are different. But the fields have similar physics that could be approached together.”

In the early days of lyophilization, pharmaceutical scientists focused on mastering the basic procedures to freeze-dry vaccines and medicines. As the field has matured, engineers like Alexeenko and her colleagues aid the effort by applying rigorous fluid dynamics, advanced manufacturing techniques and automated systems to control and optimize those environments.

Computational fluid dynamics and rarefied gas dynamics, the techniques Alexeenko uses, were originally developed for automotive and aerospace design. Fifteen years ago, Alexeenko was one of only a handful of fluid mechanic experts involved in the field. Her work and collaborations led her to co-found LyoHUB in 2014 with Elizabeth Topp, professor of industrial and physical pharmacy, in Purdue’s Birck Nanotechnology Center. Collaborators and experts in pharmacy and engineering, as well as industry members, pharmaceutical companies, software developers and equipment manufacturers, teamed up to advance the science of lyophilization.

“There’s a joke that freeze-drying is rocket science,” Alexeenko said. “But it’s hardly a joke. It is indeed complicated. It is critical to understand the science behind it and combine knowledge from many fields to build reliable systems that function under extreme environments.”

Alexeenko and her partners at LyoHUB wrote the foundational paper that stated the best practices for lyophilization instrumentation that led to the first consensus technical standard in pharmaceutical lyophilization, something they are continuing to update and evolve. Her team’s discoveries have informed the best practices used by the industry worldwide.

“Technical standards are extremely important because they save time. They save resources, and in pharmaceutical manufacturing they help save lives,” Alexeenko said. One of these lifesaving applications that researchers at Purdue LyoHUB are working on is lyophilizing mRNA lipid nanoparticle (LNP) formulations like those developed against COVID-19. The goal is to make mRNA LNP vaccines against infectious diseases and even cancers more readily available than the first-generation vaccines requiring cold storage.

When they’re not working on vaccines and medicines, the experts at LyoHUB tackle another pressing issue: snacks. Freeze-drying fruits, vegetables and other foods is a way to preserve their vitamins and nutrients while freeing them from the need to be refrigerated and preserving their shelf life.

Parents of smaller children are familiar with the fantastic, though sometimes pricey, snack of freeze-dried strawberries and bananas, while astronauts have relied on freeze-dried foods for decades. Farmers are fond of freeze-drying, especially for fruits with a short harvest season, like Indiana’s watermelons.

“We are working to make the process more efficient, more reliable, faster and more affordable,” Alexeenko said. “We have so many projects where we are working with partners to advance the technology.”

Alexeenko continues to work on her other more space-based projects as well, including a system for freeze-drying and cleaning wastewater on the space station and a very small rocket engine powered by pure water that will soon be tested on a Blue Origin spaceflight.

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