By Mark Greener, freelance medical writer

When historians of the pharmaceutical industry look back over the last 30 years, it's not only the genomic revolution and the huge innovation in rational small molecule design that will stand out. Pharmaceutical companies' innovative approaches to drug delivery will also catch their eye. Yet, today we often focus on the drug's pharmacology and miss just how radical these delivery systems can be.

Certainly, there are good commercial reasons to develop innovative delivery systems. They may attract a premium price, offer a point of differentiation in crowded markets and extend product life cycle. Yet, these are more than marketing devices. They meet real clinical needs. As we'll see, many of the new systems help R&D deliver the fruits of their labour - especially peptides and proteins - without resorting to painful injections.

More prosaically, but no less important, new drug devices can help solve clinicians' day-to-day problems - as illustrated by Zyprexa VeloTab. Compliance is notoriously poor among people with schizophrenia. This innovative new formulation of the atypical antipsychotic olanzapine dissolves in the mouth. Zyprexa VeloTab, introduced by Eli Lilly should improve compliance among people who are either unable or reluctant to swallow a standard tablet and might be especially useful in the management of acute symptoms.

Against this background, this tour can do little more than scratch the surface of drug delivery. Nevertheless, I hope it will illustrate just how innovative this area now is. We'll do this by mainly visiting sites hosted by a number of specialist delivery companies that develop the technology increasing used by large companies.

We'll start with Advanced Drug Delivery Technologies, which offers several innovative technological platforms. And these have already reached the market - its zero-order release technology for lipophilic compounds is used in Novartis' Tegretol XR - a carbamazepine formulation, for example. Another of its methods uses proliposomes. These form liposomes at the point of delivery. This overcomes some problems associated with liposome manufacture. Applications include dermal, mucocutaneous, pulmonary, oral and parenteral delivery. The company's site summarises their other proprietary technologies.

However, much of the research investigates ways to avoid the trauma of injections - with good reason. Currently, 38 of the top 100 drugs are peptides. In 1997, worldwide sales for peptide and protein drugs reached $13 billion. However, analysts expect the market to grow to $24 billion by 2002. Many of these have to be delivered using painful injections. Several new technologies avoid this.

For example, PowderJect Pharmaceuticals specialises in needle-free, pain-free injection of drugs, biopharmaceuticals and vaccines. Their system uses a brief burst of helium to accelerate fine particles of drug to high velocity. As a result, PowderJect Systems deliver pharmaceuticals and vaccines without pain or using needles.

Another approach - already marketed for some drugs for migraine and bone disease - uses nasal delivery. Currently, there are two leading niche companies developing novel nasal delivery systems. Firstly, West Pharmaceuticals have several strings to their development bow. For example, they recently started US clinical studies evaluating leuprolide in endometriosis and are preparing European registration documents before entering co-development deals. They are also developing nasal morphine that rapidly relieves pain and shows a profile similar to intravenous formulations. Clinical testing is underway.

The other major niche player Nastech - is also developing an intranasal morphine formulation as well as, among others, apomorphine for sexual dysfunction and scopolamine for motion sickness. These are lucrative markets: sub-lingual apomorphine could achieve sales of $500 million in sales by 2002 and Americans spend up to $200 million per year on motion sickness treatments. Nastech also plan to explore intranasal scopolamine as an anti-emetic in other areas.

Finally, in this whistle stop tour, we'll look at inhaled systemic drug delivery. Everyone is familiar with inhaled drug delivery for asthma and anaesthetics. However, inhaled delivery offers an effective way to deliver some systemically active macromolecules, especially proteins and peptides. Currently available platforms include:

Alkermes' AIR drug system, which delivers relatively large, low-density drug particles from simple inhalers.

Aradigm's AERx Pulmonary Drug Delivery System creates aerosols from liquid formulations. The device offers 'active breath control', which helps patients administer the medication at the correct moment.

Qdose - a UK-based collaboration between Quadrant Healthcare and MicroDose Technologies- will initially focus on delivering fast-acting insulin using the latter's hand-held, low-cost, breath-activated DPI (dry powder inhaler).

Dura's Spiros is a hand-held, battery- powered multidose system that could deliver a number of macromolecules.

Electrosols, formed at Oxford University, uses electric fields to create charged or uncharged mists

These platforms may be suitable for a variety of products including growth hormone and other peptides and macromolecules. However, inhaled insulin will probably be the first to reach the market: it is being developed by Pfizer, Aventis, Novo-Nordisk and Eli Lilly among others. You can expect inhalation to become a mainstream delivery system for macromolecules over the next few years.

Certainly, there are good commercial reasons to develop innovative delivery systems, in terms of pricing, differentiation and optimisation of new molecules' benefits. And devices can help drive your company's growth. Elan offers a case in point. Its Pharmaceutical Technologies arm has made a major contribution to the company's rapid and considerable growth. Elan Pharmaceutical Technologies uses proprietary technologies" to develop, market, and license drug delivery products to its pharmaceutical clients". Elan developed its first drug delivery technology, SODAS in the 1970s. Since then it has developed more than 20 marketed products, mainly using innovative oral systems. Today Elan is a successful, medium-sized, mainstream pharmaceutical company with an innovative R&D pipeline. In other words, drug delivery systems hone your products' competitive advantage, contribute to your company's growth - as well as offer future generations of historians something to write about.

This tour has been written by Mark Greener, a freelance medical writer. Please let us know if you have any comments or feel free to contact Mark directly by email.

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