Intended for healthcare professionals


Drug delivery from inhaler devices

BMJ 1996; 313 doi: (Published 12 October 1996) Cite this as: BMJ 1996;313:895
  1. Hans Bisgaard, Associate professor
  1. Pulmonary Service, Department of Paediatrics, Rigshospitalet, National University Hospital, DK-2100 Copenhagen, Denmark

    Lung deposition, clinical effect, and cost-effectiveness vary

    The current treatment strategy in asthma, which emphasises the early introduction of inhaled anti-inflammatory treatment,1 2 is associated with considerable additional treatment costs. The cost effectiveness of such treatment is therefore an important consideration. The purchase price of inhaled drugs is usually related to the nominal dose delivered by the inhaler, but the therapeutic effect is related to the proportion of the nominal dose deposited in the lungs. This proportion is now known to vary widely for different combinations of drugs and inhalers.

    Increased delivery of the inhaled drug to the lungs increases the therapeutic effect until the plateau of the dose-response curve is reached. This principle is the basis of adjusting doses of all inhaled drugs, including corticosteroids. However, as has been shown with the β2 agonist terbutaline, a defined clinical effect can be obtained by a certain nominal dose from one device or a by a reduced dose from a device that achieves a higher lung delivery.3 This study investigated the Turbohaler device, which delivered about twice as much of a given dose of terbutaline to the lungs as the corresponding pressurised metered dose inhaler. This finding has been confirmed for the Turbohaler delivering terbutaline and budesonide in short and long term clinical studies,3 4 pharmacokinetic assessments,5 in vitro studies,6 and scintigraphic studies.7 Although doubling the nominal dose given via a pressurised metered dose inhaler may produce a therapeutic effect similar to that achieved with a Turbohaler, more of the drug would be wasted and the treatment cost would be doubled.

    Similar differences in cost effectiveness are apparent among the recently developed small volume spacers for use with pressurised metered dose inhalers in young children. The comparative efficiency of the spacers has been documented in vitro8 and in vivo9 by measuring the fine particle fraction of the aerosol delivered from the inhaler and spacer unit in filters positioned in front of the inhaler's respiratory valve. Although the fine particle mass is not a measure of lung deposition, it is generally agreed that it provides the best estimate of the dose likely to reach the lungs.10 During simulated breathing by a ventilator, the relative fine particle masses delivered by a pressurised metered dose inhaler plus a NebuChamber spacer (budesonide), an inhaler plus Babyhaler (fluticasone), and an inhaler plus AeroChamber (budesonide) were 1, 1.5, and 2.5 respectively.8 This suggests that the nominal dose for an inhaler plus AeroChamber should be 2.5 times higher than that for an inhaler plus NebuChamber to obtain the same clinical effect. Further in vivo data are needed to confirm these findings, but these studies highlight the influence of the spacer device on the fine particle mass delivered and thus on the cost effectiveness of treatment. Differences in cost due to loss of aerosol are likely to outweigh any difference in the initial cost of the inhaler device.

    The use of various low cost containers, such as a disposable coffee cup, or of a large volume spacer and face mask in conjunction with a pressurised metered dose inhaler has been suggested as an inexpensive means of providing inhaled drugs in young children,11 12 and the use of such low cost devices has been supported by the British guidelines on managing asthma.2 However, the fraction of the nominal dose delivered from these devices is low and variable,13 and total cost of treatment would probably be high as a result of the high waste of the drug.

    As the clinical effect, systemic activity, and cost effectiveness of treatment with topical corticosteroids is mainly related to the dose delivered to the lungs,14 future recommendations and assessments of costs should be based on the dose likely to reach the lungs rather than on the nominal dose. This dose is largely dependent on the device used. Many countries have strict regulations concerning oral formulations of drugs, which require the manufacturer to establish the bioavailability of a drug before a product licence is granted. However, there are few regulations governing the efficiency of inhalation devices, and the proportion of the nominal dose delivered to the lungs by a device is seldom evaluated. Indeed, the fact that changing the device used to deliver a drug will have a major impact on drug bioavailability is rarely considered by regulatory authorities or prescribers.

    In future, product licences should be restricted to specific combinations of drug and device, supported by thorough documentation. Recommended doses should similarly be based on lung bioavailability rather than nominal dose, emphasising the fact that the drug and device must be considered as a single entity. Such an approach should lead to the more effective and safe use of inhaled drugs and to more realistic estimates of the relative cost effectiveness of different treatments.


    • Drug potency varies widely when different inhalation devices are used

    • Therefore, clinical effect, systemic activity, and cost effectiveness of treatment varies for the same drug if delivered by different devices


    • Prescribers must consider drug and device as single entity

    • Dose recommendation should define the device

    • Dose recommendations and estimates of cost effectiveness should relate to likely lung dose rather than nominal dose

    • Licensing should be restricted to specified combinations of drug and device


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