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Jenny Bryan is a freelance writer based in London
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The lungs are a lucrative target for pharmaceutical companies developing
novel drug delivery systems for asthma and COPD |
If you are designing a new inhaler for lung disease, do you put your
money on dry powder or metered-dose inhalers, more accurate dosing or
more efficient deposition, innovative mechanism or tried and tested reliability,
patient friendliness or just plain old price? If you thought the inhaler
market was already too overcrowded to be asking such questions, think
again. In a market worth around £3bn, at least a dozen big and
small name pharmaceutical companies are
developing drug delivery systems for asthma and chronic obstructive pulmonary
disease which could soon be coming to your
pharmacy.
“In Europe there’s been a push towards dry powder devices, and MDIs
took a big knock because of the environmental issues, but they’ve
still got the advantage that they’re so robust,” says Glyn
Taylor, senior lecturer at the Welsh School of Pharmacy in Cardiff.
However, he sees cost as a continuing and major hurdle for companies
intent on designing something truly novel.
“The regulatory agencies see devices and drugs in different budgets, and
they take a narrow view of what devices they will pay for. But there
could be huge savings to be made from reduced hospital admissions for
asthma and COPD patients if you can show that a device gives you better
drug deposition or patients are using it more effectively,” adds
Dr Taylor.
Others debate the importance of better drug deposition for asthma and
COPD. There is little disagreement about the need to get 70 per cent
of a dose deep into the lung for treatment of systemic diseases, such
as diabetes (see PJ, 31 July 2004, pp161–2), but some consider
that the 10–40 per cent achieved with the highly potent steroids
and bronchodilators currently used to treat asthma and COPD may be enough.
Even so, in certain situations, such as treatment of lung infections
with antibiotics or, in the future, cystic fibrosis with gene therapy,
high dose delivery may be desirable.
At the University of Bath, Paul Young and his colleagues in the Pharmaceutical
Technology Research Group, in the Department of Pharmacy and Pharmacology,
recently showed that it is possible to achieve 70 per cent efficiency
in delivering a high dose treatment, such as surfactant, into the lung,
using pressurised gas to aerosolise dry powder in a hand-held inhaler.1
Another novel inhaler that has moved away from tried-and-tested delivery
systems is Boehringer Ingelheim’s Respimat Soft Mist Inhaler (SMI).
Already on the market in Germany as a delivery device for the combination
of fenoterol and ipratropium bromide, Respimat is a propellant-free,
liquid-based device which produces a slow moving mist of drug.
According to Boehringer Ingelheim, the soft mist travels more slowly
and lasts much longer than aerosol clouds from traditional devices, and
scintigraphic studies show that this leads to more drug deposited in
the lungs and less in the mouth and throat than with an MDI. A recent
review of clinical trials suggests that it may be possible to reduce
the dose of ipratropium/fenoterol required, for the same efficacy than
when treatment is inhaled through a chlorofluorocarbon MDI.2 Patient
preference studies, presented by the company at last year’s European
Respiratory Society conference in Glasgow, showed that patients preferred
Respimat over conventional devices. But no date has been set for a UK
launch.
SkyeHaler — a dry powder inhaler developed by drug delivery specialists
SkyePharma — has received EU approval for use with Novartis’s
formoterol, and is expected to receive individual country approvals this
year. It uses magnesium stearate to protect dry powder drugs from moisture
and, in the case of formoterol, to help bulk-up the low doses that are
required, so that flow and deposition can be improved.
Magnesium stearate is also being used in SkyePharma’s hydrofluoroalkane
MDI, not only as a bulking agent, but also as a lubricant to reduce valve
wear and tear — a common cause of inhaler failure with HFA devices.
Completing the company’s range of novel inhalers is an HFA MDI
which uses sodium cromoglicate, not as an active ingredient, but as an
excipient to scavenge moisture.
“We looked at a lot of different drugs and excipients and it turned out
that sodium cromoglicate was the most hygroscopic compound we tested.
So given its safety record, we decided to use it in our MDI,” explains
Geraldine Venthoye, business unit lead, aerosol and inhalation at SkyePharma.
The Achilles heel of many dry powder devices is the energy which patients
need to generate to get the drugs into their lungs, and companies, such
as SkyePharma and Nektar Therapeutics, are quick to show how they have
overcome this problem. For example, the Nektar Pulmonary Inhaler is powered
by a bolus of compressed air to make drug delivery independent of inspiratory
air flow, and powder is dispersed into a holding chamber from which the
patient inhales.3
Like many of the new generation of inhalers, the Nektar device includes
an indicator to show when a dose has been taken. Better feedback to patients
about how well they are using their inhaler is another area of interest
among developers of novel inhalers.
Perhaps the most adventurous attempt at getting asthma patients to take
more interest in the way they use their inhalers is SmartMist — a
microprocessor controlled device which allows actuation of an MDI at
a preprogrammed point during inspiration, with a traffic light system
to signal when patients have inhaled correctly. It also measures lung
function, with a downloadable record of results.4,5
But innovation alone is not enough to get the pharmaceutical industry
to pay serious money to take a novel inhaler through to market. For those
making and selling millions of inhalers every year to service a worldwide
market, device reliability is even more important than innovation. A
failure rate of just 0.1 per cent can mean hundreds of thousands of treatment
failures — and complaints — and is not acceptable to the
big league. But device reliability is hard to prove when all you have
is a prototype.
Pulmonary product development company, Vectura, appears to be responding
to real-world need for low cost, reliable devices rather than innovation,
with its new 60-dose, dry powder Gyrohaler. It boasts the simplicity
of its new device, which has fewer than 10 simple mouldings, and, it
says, is smaller, lighter and likely to be less expensive than other
dry powder devices.
Whether it can compete with the success of another small devices company,
Meridica, remains to be seen. So impressed was Pfizer with Meridica’s
inhalation technology that it recently bought the company — for
a reported $125m. Small pharmaceutical companies undoubtedly know there
is money still to be made from novel inhalers — as long as they
can balance innovation against price.
References
1. Young PM, Thompson J, Woodcock D, Aydin M, Price R. The development
of a novel high-dose pressurized aerosol dry-powder device (PADD) for
the delivery of pumactant for inhalation therapy. Journal of Aerosol
Medicine 2004:17:123–8.
2. Kassner F, Hodder R, Bateman ED. A review of ipratropium bromide/fenoterol
hydrobromide (Berodual) delivered via Respimat Soft Mist Inhaler in patients
with asthma and chronic obstructive pulmonary disease. Drugs 2004;64:1671–82.
3. Chan H-K, Chew NYK. Novel alternative methods for the delivery of
drugs for the treatment of asthma. Advanced Drug Delivery Reviews 2003;55:793–805.
4. Gonda I, Schuster JA, Rubsamen RM. Inhalation delivery systems with
compliance and disease management capabilities. Journal of Controlled
Release 1998;53:269–74.
5. Farr SJ, Rowe AM, Rubsamen R, Taylor G. Aerosol deposition in the
human lung following administration from a microprocessor controlled
pressurised metered dose inhaler. Thorax 1995;50:639–44. |
The
Pharmaceutical Journal