Postdoc Peter Ouma Okeyo and his colleagues at DTU Health Tech, University of Copenhagen and University of Oslo have developed a new method that can reduce costs in early drug development.
In early drug development and biomedical settings, it is imperative to perform a comprehensive analysis of the material to prevent unwanted changes. It is easy to imagine that if a drug’s properties and thus its effect changes because of temperature changes, then the pharma company behind the drug should be aware of the consequences. If thorough investigations have not been performed with the pure drug before releasing it to the consumers, a pharmaceutical company could be faced with delayed development times or forced to withdraw the drug from the market, something that could be a costly affair not only financially but also image-wise.
Changing materials properties
An example of a material that changes properties due to a change in the environment is a piece of cardboard. In its original state, it is quite stiff and robust, and the surface is smooth. If the cardboard gets wet, then its properties changes, i.e. it becomes soft and loses its strength. But if it is dried again, its properties do not return to the point of departure. Instead, it often gets a slight curve, and the surface becomes uneven. For drugs, which for example are stored in a cabinet in a bathroom where the surroundings can change rather much in terms of both temperature and humidity, it is important to know what effect this may have on the drug’s properties.
Thermal analysis
Thermal analysis is used to investigate the effect of temperature on a drug and to understand its physical stability (in order to prevent unwanted phase transformations during development, manufacturing and storage). However, standard techniques require a minimum of several milligrams of material, and will give an averaged response on the measured material. This means that it is not possible to determine the thermal response of a single particle. An approach that is being investigated is based on microelectromechanical systems (MEMS) that require much smaller sample sizes (nano-microgram) of the drug, and thus allow for the analysis of a single drug particle. The problem is that this method requires access to specialized clean-room facilities and specialists. For pharmaceutical scientists it can be a challenge to get access to such facilities, which is also a large entry in the budget, not only for small companies but also for larger companies.
The new PMTA method
Peter Ouma Okeyo, who is a Postdoc in Professor Anja Boisen’s research centre IDUN at DTU Health Tech, has headed the development of a new method that is called Particle Mechanical Thermal Analysis (PMTA). PMTA bypasses the barrier described above, by using the drug material itself as a MEMS device. Hereby, it is possible to do analysis directly on a single particle of drug. This means that any impurities that may have been in the larger bulk of material that is needed for standard methods can now be filtered out and the analysis will can be done more accurately on a pure drug particle.
Furthermore, the new method has also provided additional insights into thermal transitions, which are undetected by standard methods, showing potential towards providing us with a unique understanding of the fundamental changes in mechanical properties of a material under different thermal conditions.
Finally, another very interesting feature of the method is that it makes access to clean-room facilities obsolete, as it can be conducted in an ordinary lab.
If you are interested in more details about the research, read more in the newly published paper in Nature Communications
Single drug particle as a resonator (cantilever). Photo by Jesper Scheel.
Caption top image: Postdoc Peter Ouma Okeyo shows needle drug particles in a solution. Photo by Jesper Scheel.
PMTA works by essentially tracking the resonance frequency of the measured particle during thermal cycling. The changes in the resonance frequency can be related to mass and mechanical related changes occurring in the particle. An illustration of a resonance frequency is with a guitar that has different sounds when different strings are struck.