Analysis: Researchers are exploring how protein crystals produced in a zero-gravity environment like space could lead to more effective drugs
In 1969, during the first Moon landing, Neil Armstrong's words echoed from the lunar surface to mission control in Houston and are still remembered to this day: "That’s one small step for man, one giant leap for mankind." That leap into the unknown paved the way for many further incremental strides forward. Telecommunications and environmental observation satellites orbit the Earth every day, while astronauts on the International Space Station conduct research under the effects of microgravity. The advent of commercial, reusable rockets has significantly reduced launch costs, making space more accessible than ever.
Another promising development for our everyday lives may come from the manufacturing of pharmaceutical drugs in space. To understand the logic behind this, we need a quick glimpse into crystallization processes, a crucial step in pharmaceutical drug development. In this process, solid crystals of a drug compound are obtained from a liquid solution containing the drug in dissolved form in a way that purifies and isolates the active pharmaceutical ingredients. During production and storage, one must carefully control factors such as temperature, cooling rate, pressure and dissolved drug concentrations to influence the crystal’s size, shape and form.
Gravity is challenging to control in a laboratory, especially when it comes to creating a low-gravity or microgravity environment.
The influence of manufacturing parameters on the crystalline structure can cause the same substance, with the same chemical composition, to organize itself into different crystal forms. This phenomenon, known as polymorphism, can significantly affect the drug’s effectiveness in treating disease and its safety for patients.
One famous example is the case of ritonavir, an important HIV drug that accidentally crystallized into a new polymorph, which replaced the original form, during manufacturing in 1998. This change significantly affected the drug’s properties. The new polymorph was less stable, had increased solubility, and crucially did not have the same therapeutic effect as the original form, forcing the laboratory to temporarily withdraw the drug from the market. The company suffered major losses, and the incident prompted the pharmaceutical industry to monitor polymorphic changes in drug development to avoid similar costly problems.
While many factors influence polymorphism, gravity is particularly challenging to control in a typical laboratory, especially when it comes to creating a low-gravity or microgravity environment. The weightlessness experienced aboard spacecraft may allow scientists to grow crystals with better properties than under standard Earth-based lab conditions. US company Varda Space Industries has already launched experiments into Low Earth orbit and retrieved the results for analysis.
Understandably, conducting many experiments to explore the full potential of microgravity environments for drug crystallization can be costly. This is where research at the University of Limerick comes into the picture. By developing advanced equations to describe crystal growth and running computer simulations, we are studying crystallization in microgravity environments. Our work aims to improve our understanding of how different polymorphs form and how reduced gravity could enhance control of this process, with the goal of helping to create better medicines on Earth.
Those equations were applied to study the crystallization of a substance with two known polymorphic forms, A and B, with A being the most stable. The video below illustrates the formation of both polymorphs during crystallization under different gravity conditions.
It was found that the amount of a specific polymorph in a system under altered gravity can be up to 20% higher than that observed under Earth's gravity at a given time. Moreover, it is seen that at later stages, the less stable form B dissolves, allowing continued growth of the more stable form A, like the polymorphic conversion of ritonavir in the case of 1998.
Nucleation and growth of two different polymorphs under different gravity conditions
Could microgravity really improve crystallization?
Several experiments conducted onboard the International Space Station have shown that crystals grown in microgravity are often larger and more ordered than those grown on Earth. The improved quality of these space-grown crystals allows scientists back on Earth to analyze their structures more clearly, advancing our understanding of crystalline materials. Scientists believe that these advantages arise from the slower, more uniform movement of molecules into crystalline lattice in microgravity conditions.
Research on crystal growth in space holds significant potential to benefit life on Earth across various applications. Additionally, well-tailored mathematical models can help reduce the number of experiments needed - especially given the current difficulty of accessing these orbiting laboratories - thereby speeding up and reducing costs in drug development conducted in space.
This research is supported by Taighde Éireann/Research Ireland through the SSPC Research Ireland Centre for Pharmaceuticals in partnership with Varda Space Industries
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The views expressed here are those of the author and do not represent or reflect the views of RTÉ
