Method to predict drug stability could lead to more effective medicines

Researchers from the UK and Denmark have developed a new method to predict the physical stability of drug candidates, which could help with the development of new and more effective medicines for patients. The technology has been licensed to Cambridge spin-out company TeraView, who are developing it for use in the pharmaceutical industry in order to make medicines that are more easily released in the body.

This is a very old problem, and for pharmaceutical companies, it’s often too big of a risk.
- Axel Zeitler

The researchers, from the Universities of Cambridge and Copenhagen, have developed a new method to solve an old problem: how to predict when and how a solid will crystallise. Using optical and mechanical measuring techniques, they found that localised movement of molecules within a solid is ultimately responsible for crystallisation.

This solution to the problem was first proposed in 1969, but it has only now become possible to prove the hypothesis. The results are reported in two papers in Physical Chemistry Chemical Physics and The Journal of Physical Chemistry B.

Solids behave differently depending on whether their molecular structure is ordered (crystal) or disordered (glass). Chemically, the crystal and glass forms of a solid are exactly the same, but they have different properties.

One of the desirable properties of glasses is that they are more soluble in water, which is especially useful for medical applications. To be effective, medicines need to be water-soluble, so that they can be dissolved within the body and reach their target via the bloodstream.

“Most of the medicines in use today are in the crystal form, which means that they need extra energy to dissolve in the body before they enter the bloodstream,” said study co-author Professor Axel Zeitler from Cambridge’s Department of Chemical Engineering & Biotechnology. “Molecules in the glass form are more readily absorbed by the body because they can dissolve more easily, and many glasses that can cure disease have been discovered in the past 20 years, but they’re not being made into medicines because they’re not stable enough.”

After a certain time, all glasses will undergo spontaneous crystallisation, at which point the molecules will not only lose their disordered structure, but they will also lose the properties that made them effective in the first place. A long-standing problem for scientists has been how to predict when crystallisation will occur, which, if solved, would enable the widespread practical application of glasses.

“This is a very old problem,” said Zeitler. “And for pharmaceutical companies, it’s often too big of a risk. If they develop a drug based on the glass form of a molecule and it crystallises, they will not only have lost a potentially effective medicine, but they would have to do a massive recall.”

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Image:Medication

Credit: Gatis Gribusts

Reproduced courtesy of the University of Cambridge



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