The challenge of delivering drugs to the lungs

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The pulmonary route has an established role in the treatment of asthma and chronic obstructive pulmonary disease (COPD), and has a number of other topical and systemic applications. Successful pulmonary drug delivery requires a predictable, reproducible lung dose and clinical effect with each treatment, while minimising unwanted side-effects, and achieving these objectives at reasonable cost. The patient presents a major barrier to achieving these goals, first because of natural lung defence mechanisms, and second because of the need to use, and to master the use of, an inhaler device. The respiratory tract has evolved in such a way as to prevent the ingress of particles and droplets, and to remove inhaled materials once deposited. Formulators strive to ensure that an adequate fraction of the delivered dose consists of particles within the fine particle range (< 5 µm) for whole lung deposition, and < 3 µm for peripheral lung deposition. Once deposited, drugs may be removed from the lungs by mucociliary clearance or by phagocytosis, or may be degraded by the action of proteases. Each patient must use an inhaler as prescribed (i.e. be adherent to the treatment regimen), and must use it correctly (i.e. prepare the device for inhalation, and then inhale from it in an appropriate way). Poor adherence and inhaler misuse are widespread problems, which can be addressed via appropriate selection of an inhaler, via use of other technology, and via education. Selection of an inhaler also needs to take into account the mass of drug to be delivered; pressurized metered dose inhalers (pMDIs) and many dry powder inhalers (DPIs) are unsuitable for delivering drug doses > 1 mg. Efficient inhalers delivering a high percentage of the drug dose to the lungs generally provide the most reproducible lung dose. The pulmonary route is a relatively complex one, but the advantages it offers justify its use for a range of treatment indications.

01.Newman