Innovation: Glaxo backs Bradford's laboratory revolution

GLAXO, the UK's leading drug company, believes that a new process developed at Bradford University will transform its manufacturing techniques.

The process, on which Glaxo and the university share a patent, is a precise way of controlling the formation of drug particles. This ensures higher purity, cuts out secondary processing, and could allow the company to switch from batch to continuous production.

The process could also be applied in other sectors of the chemical industry to cut manufacturing costs and reduce pollution levels.

Conventional drug production is essentially no different from a school chemistry experiment - if more refined and on a larger scale. The ingredients, including a solvent, are mixed in a reaction vessel rather than a test-tube. To start the reaction, the mixture may be heated or put under pressure, and at the end of the reaction the product is crystallised to separate it from the solvent and remove any by-products.

It is extremely difficult to remove the solvent and the impurities completely, so there is usually a tiny percentage of each in the final drug.

In addition, many solvents are organic chemicals, which are toxic and inflammable, and which cause pollution if they are not disposed of properly.

The Bradford process, developed by Peter York and colleagues in the School of Pharmacy, gets round the solvent problem by dissolving the ingredients in liquid - or supercritical - carbon dioxide. This drastically reduces the amount of solvent needed.

The solvent and any impurities have an affinity for the supercritical carbon dioxide, which sucks them out of the reaction mixture. They are deposited at the end of the cycle when the carbon dioxide becomes a gas again. 'The system beats as it sweeps as it cleans,' says Professor York.

Glaxo is now sponsoring the university to engineer an industrial-scale system. David Rudd of Glaxo said the technique could be applied to the company's drug-manufacturing business as soon as this project was completed.

Carbon dioxide and other gases become supercritical - acquiring a mixture of liquid and gas properties - when they are simultaneously pressurised and heated. Although supercritical carbon dioxide is inert and non- toxic, it will dissolve substances that normally dissolve only in toxic organic solvents. The best- known use of supercritical carbon dioxide is in food- processing, where it is used to dissolve out caffeine from coffee beans.

Until this method was developed in the 1960s, the only way to decaffeinate coffee was to use organic solvents that leave toxic residues.

Apart from overcoming the problems associated with solvents, the Bradford system will enable particle characteristics, such as size and shape, to be manipulated precisely. The solvent properties of supercritical carbon dioxide are altered by subtle changes in temperature and pressure. This affects the rate of reaction and modifies the end product. This will allow Glaxo to avoid the potentially damaging and costly secondary processing used in conventional drug production.

Asthma drugs, for example, have tiny particles 1-3 microns long, enabling them to reach the deep recesses of the lungs. 'It is very difficult to produce these directly, because you can't completely filter the solvent away from such small particles,' Professor York said.

Larger particles are milled down, but this often creates another problem, as the minute particles are attracted to each other and form clumps which block machinery. Milling can also change the physical and structural properties of a drug. In some cases the crystal structure is deformed, allowing water or oxygen to enter, and reducing the shelf-life.

Mr Rudd said that if the work to scale up the process was successful, it should be possible to produce asthma drugs as a one-stage process, including the packaging of drugs in blister packs.

(Photographs omitted)