New method developed to predict drug stability

New method developed to predict drug stability

Researchers have developed a new method of testing how stable potential drugs will be, before they are put into production and cost manufacturers millions of pounds.

The team from the Universities of Cambridge and Copenhagen wanted to be able to predict how and when solids will crystallise, as this affects whether or not they will be capable of dissolving in the bloodstream.

Using optical and mechanical measuring techniques including terahertz spectroscopy, it was discovered that it is the localised movement of molecules within a solid that is ultimately responsible for crystallisation, rather than the transition temperature.

In order for new drugs to be developed, research has to be carried out into their molecular structure and whether it is crystal or glass. This is important because, although there is no difference in the molecules contained within, the properties are very different.

Glasses are extremely soluble in water, which is good for medical applications because it means they can easily be absorbed into the bloodstream.

However, study co-author Professor Axel Zeitler explained that most of the drugs in use today are in crystal form, because glasses are more unstable and it has previously been impossible to know when they will solidify or crystallise and thereby lose their useful properties.

"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. 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," he added.

As a result, crystals are widely used - but they require extra energy to dissolve in the body before they enter the bloodstream.

The researchers wanted to see if they could predict when the crystallisation of glasses would occur, thereby making it possible to put them to better use within the healthcare industry.

Writing in the publications Physical Chemistry Chemical Physics and The Journal of Physical Chemistry B, the team revealed that they have now successfully achieved this and were able to use a calibration curve focusing on localised molecular movements to predict how long it would take glass materials to crystallise.

The technology has now been licensed to TeraView and it is being developed for use in the hope that it will lead to more medicines that are able to be easily released in the body.

Many drug molecules that were previously discarded for lack of stability are also likely to be re-tested to see if they can be brought to the market in a more stable form that is more effective than their crystal counterparts.

One medicine that was famously subject to a recall due to lack of stability in its structure was Ritonavir, a HIV treatment released in the US as Norvir in 1996.

Precipitates began to form in the product and it became less soluble, meaning it was less effective at getting into the bloodstream and less potent as a treatment. The product had to be recalled and redeveloped at a cost of millions of dollars to the manufacturer.