ReviewThe inhalers of the future? A review of dry powder devices on the market today
Introduction
Over 40 years have elapsed since the pressurised metered dose inhaler (pMDI) was first introduced as a convenient delivery system for targeting bronchodilator drugs, and later corticosteroids, directly into the lungs of patients with asthma [1], [2]. Now, at the dawn of a new era and in light of the seemingly inexorable worldwide socio-economic impact of chronic respiratory diseases, environmental concerns over the use of propellant gases have forced the pace of pharmaceutical research into suitable replacements for the CFC-pMDI [3], [4], [5], [6]. Major constraints include the need for improved patient compliance and cost-effectiveness of treatment [7], [8]. Various approaches appear to offer feasible solutions to the problem, with current developments concentrating largely in the two major areas of pMDI reformulation and innovative DPI technology. Successful reformulation with ‘ozone-friendly’ hydrofluoroalkane (HFA) propellants will permit the continued use of some drugs in the pMDI in the shorter term, and patient coordination difficulties may be resolved by means of breath-actuated pMDIs as well as spacers or valved holding chambers [6]. The reality of global warming continues to escalate, however, potentially limiting reliance on propellant-based pMDIs in the longer term. In practice, the patient-driven, propellant-free, multiple-dose DPI is most likely to emerge as the device of the future for the control and management of asthmatic disease [6], [7], [8]. These inhalers are inherently both environmentally friendly and more user friendly, holding the prospect of more effective therapy through improved compliance. This review therefore focuses on the multiple-dose DPIs which are commercially available today.
Section snippets
Profile of the traditional pMDI as historic ‘gold standard’
Since its introduction in 1956, the pMDI has been the system of choice for delivery of inhaled therapies for airway diseases such as asthma [1], [9], [10]. The chief advantage in targeting drugs directly into the lung lies in reduction of systemic bioavailability, and consequently of unwanted side-effects. The most frequently used classes of drug, β2-agonist bronchodilators and corticosteroids, both have dose-related adverse systemic effects and dosage should therefore be kept to a minimum [10]
Green—or greenhouse?
Replacement of the CFC-driven pMDI is no longer an option but a necessity. Concerns over damage by chlorine to the Earth's ozone layer, due to the accumulation of CFC gases in the stratosphere, came to light almost 30 years ago [36]. The ozone layer plays an essential role in absorbing ultraviolet-B rays, thus preventing potentially devastating over-exposure of plant and animal life-forms to short wavelength radiation from the sun. When fears of its impending destruction were confirmed by the
First phase of DPI development
In response to the need for effective asthma drug delivery alternatives to pMDIs, three multiple-dose inhaler devices were developed by multinational pharmaceutical companies AstraZeneca (Turbuhaler/Turbohaler) and GlaxoSmithKline (Diskus/Accuhaler and Diskhaler), for their own bronchodilator and corticosteroid treatments. Other bronchodilator therapies have since been made available via the Turbuhaler device.
Turbuhaler
The AstraZeneca Turbuhaler (Fig. 1) is made up of 13 plastic components and a steel
Diskus versus Diskhaler
Interpretation of comparative studies is problematic in that not only the device, but often a different drug and a different formulation must be taken into account. This holds true irrespective of DPI/pMDI or DPI/DPI comparisons. At the same time, more sophisticated techniques of in vitro assessment have become the norm [33], [34].
The results obtained by Srichana et al. [60] caution against extrapolation of in vitro performance data from one drug/device combination to another: the salbutamol
Conclusion
A summary outlining the major design and performance features of the six DPI devices detailed in this review (based on the published information) is presented in Table 2. One of the main disadvantages associated with single-dose DPIs, in addition to patient handling issues involved with capsule reloading, is poor efficiency of lung delivery, with as little as 10% of the dose reaching the lung. Deposition of the inhaled aerosol from DPIs is influenced by both the patient and the physical
Acknowledgements
We gratefully acknowledge the contribution made by Patsy Riley in producing this review.
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