
Researchers at Chalmers University of Technology, the Paul Scherrer Institute (PSI), and EPFL have, for the first time, utilised powerful X-ray imaging techniques to investigate drug formulations.
“Nobody has previously employed these synchrotron-based techniques in this context, and we find the results fascinating. This method could be directly applied in the development and research of drug formulations,” says Professor Aleksandar Matic.
When a tablet releases a drug into the body, the release rate should vary depending on the desired therapeutic effect. Therefore, understanding the mechanisms controlling release and stabilising drug substances in a polymer matrix, a common material in drug formulations, is crucial.
X-rays reveal drug release mechanisms
The researchers have demonstrated that advanced synchrotron-based X-ray imaging techniques can be used to study the structure of formulations to better understand drug release processes. They have also developed a material concept, a polymer matrix, where the structure and composition govern release mechanisms.
The research findings are published in Communications Materials, an open-access journal from the Nature Portfolio. The study was led by Professor Aleksandar Matic from the Department of Physics at Chalmers, and Marianne Liebi, Associate Professor at PSI/EPFL and Affiliate Docent at Chalmers. The project was conducted by PhD student Martina Olsson as part of her Excellence PhD position within Chalmers’ Area of Advance Nano.
3D imaging of drug formulations
What makes this synchrotron-based X-ray technique unique in this context is its ability to produce 3D images that depict structures with a resolution of 100 nanometres.
“We show that this type of X-ray technology can be used to understand these materials. There is great potential for drug formulation development using these powerful techniques, as they offer new ways to examine materials in detail. You can explore the material with very high contrast and in 3D volumes comparatively larger than other methods allow,” says Martina Olsson.
“We provide a new tool for formulation development, not only for pharmaceuticals but also for other products where controlled release from a matrix is key. The methods may seem advanced, but they can be applied immediately to solve relevant problems,” adds Aleksandar Matic.
Designing a unique material concept
The material concept studied during the X-ray experiments was proposed and developed by Anette Larsson, Professor at the Department of Chemistry and Chemical Engineering at Chalmers. The concept involves a phase-separated polymer matrix composed of two polymers: one water-soluble (HPMC) and the other less water-soluble (PLA). The material is designed as a labyrinth that ensures optimal drug release for the body to absorb effectively.
“In polymer-based drugs, there are many intriguing phenomena that remain poorly understood, such as release mechanisms. This is what we aim to resolve using X-ray techniques,” says Martina Olsson.
The researchers examined various material compositions and how their structures influence drug release. By visualising nano- and microstructures, they gained deeper insight into the release processes.
“Thanks to the highly detailed images, we can understand the material’s function significantly better. For instance, we can distinguish between polymer phases and the drug in great detail. X-ray imaging often struggles to differentiate between components with similar chemistry, but this technique enables us to detect very fine differences,” explains Olsson.
Next steps: studying the material during drug release
After characterising the material’s structure, explaining the release processes, and developing methods and data analysis, the researchers now aim to study the material in real-time as it releases in a buffer solution.
“We want to study the material in a buffer that mimics the body’s environment. What happens over time as water penetrates the material? How do the different components respond? These are questions we intend to explore in future experiments,” concludes Aleksandar Matic.
This is synchrotron radiation
Synchrotron light, also called synchrotron radiation, is produced by accelerating electrons to near the speed of light in a circular orbit. The electrons are deflected by magnetic fields and generate extremely bright X-ray light. A synchrotron facility is a large-scale facility that produces this type of radiation and where experiments take place in beamlines. These beamlines are highly specialized laboratories equipped with state-of-the-art instruments.
The main difference between synchrotron light and the X-rays produced by lab sources and in hospitals is the brilliance: a synchrotron source is about one hundred billion times brighter than a lab-scale X-ray source. With higher brilliance, more precise information can be obtained from the X-rays which enables experiments to be conducted with very high speed and resolution. Synchrotron radiation is applied to study materials in a wide variety of fields e.g. material physics, chemistry, for medical applications, cultural heritage and energy applications.
Source: ESRF - The European Synchotron
About the research:
- The scientific article “Phase-separated polymer blends for controlled drug delivery by tuning morphology” was published in Communications Materials on October 18 2024, and is written by Martina Olsson, Robin Storm, Linnea Björn, Viktor Lilja, Leonard Krupnik, Yang Chen, Polina Naidjonoka, Ana Diaz, Mirko Holler, Benjamin Watts, Anette Larsson, Marianne Liebi and Aleksandar Matic.
- The researchers are active at the Department of Physics and the Department of Chemistry and Chemical Engineering at Chalmers University of Technology; the Paul Scherrer Institute in Switzerland; EPF Lausanne, and Swiss Federal Laboratories for Materials Science and Technology.
- The experiments were performed at Swiss Light Source (SLS) at the Paul Scherrer Institute.
- See a presentation where Martina Olsson discusses X-ray imaging and speaks about an example from the scientific article: X-ray imaging in material science by Martina Olsson (Youtube)
The illustration is published under the Creative Commons license.
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