A spoonful of sugar helps the medicine go down

Cooper James looks at the development of a pharmaceutical process that could dramatically change the way in which drugs are taken and stored
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The Independent Online
Who would have thought that Mary Poppins would prove an inspiration to the international pharmaceutical industry? Yet the drugs manufacturers appear to be adding a hi-tech twist to her adage that "a spoonful of sugar helps the medicine go down".

It may not make a musical number, but a new process could radically change the way drugs are used and stored, and possibly make every child's nightmare - the hypodermic needle - a thing of the past. By introducing a form of sugar into a drug solution and then freeze-drying it, the drug can be turned into a stable, glassy material that retains all its medicinal properties when rehydrated.

If the process can be developed and made widely available, it could prove to be a massive boon to hospitals and surgeries, as many of the drugs they use on a daily basis - such as the common vaccinations for tetanus, polio, typhoid, hepatitis and yellow fever - are kept in solution. But in this state they are vulnerable to a wide range of degrading chemical reactions and have to be stored at between 2C and 8C in expensive refrigeration units. Even then, they have a relatively short shelf-life. The need for constant refrigeration also limits the transportation and use of drugs in many areas, especially in some Third World countries, where electricity supplies may be unreliable.

The process that could change all this has been developed by Pafra, a company based in Cambridge University Science Park. It relies on the application of naturally occurring techniques. Some plants, insects and micro-organisms that regularly have to face the threat of extreme dehydration - such as saltwater worms living in tide pools, or the resurrection plant, anative of the North American desert - have evolved a method of converting their body starches into sugars when they begin to dry out. As the water leaves, their tissue becomes more and more viscous until eventually their bodies turn into a brittle, glassy solid. The crucial aspect of this solid state is that it is achieved without any crystallisation, which would destroy the very cells that need to be maintained until such time as the tissue can be rehydrated.

Pafra's Dr Felix Franks teamed up with Dr Lindsey Greer, a specialist on glass materials based at Trinity College, Cambridge, to explore the possibilities of artificially reproducing this process with unstable biological reagents and compounds that normally exist in solution in water - drugs and enzymes being the prime examples. By buffering the drug solution with various sugars before freeze-drying, the natural process can be mimicked. As the solution dries, it hardens by forming glassy molecular rods rather than crystals, and these rods return to their previous form when rehydrated. In such a vitrified compound the chemical reactions that degrade solutions - and are the reason why they have to be kept refrigerated - are almost totally stifled. As a result, the freeze-dried drug is stable at relatively high temperatures and has a markedly increased shelf-life.

The dehydrated material is correctly described as a glass. Window glass itself does not have a crystalline form but is technically a liquid, and does exhibit flow over long periods of time. Non-crystalline dehydration can also be found in a commonly used product such as spaghetti, which in its dry form has long molecules and a glassy structure and therefore softens when added to water, rather than dissolving as it might be expected to do.

Pafra is licensing its process to larger companies such as Pharmacia, the Swedish biotech firm, and Inhale Therapeutics, a Californian company engaged in developing means of administering drugs by deep lung inhalation - an effective alternative to injection for delivering a compound into the bloodstream. They are interested in the dried drugs because they need a stable product that can be turned into a "smoke" and breathed in. Although enzyme vitrification is not far off, it is likely to be some while before we see the widespread use of drug vitrification, given the length of time needed for the validation of new drugs and storage mechanisms.

As Dr Franks points out: "The properties of water-soluble glasses is a whole new field of science, and one that we still do not know much about." Yet he and Dr Greer remain optimistic that the process will have an important impact in the long run, given the lack of refrigeration in many parts of the world and the benefits of being able to carry and store medical drugs in a stable, solid form.