Anatomy and physiology in delivery: can we define our targets?

Studies have shown that the receptors for beta-agonists, inflammatory markers, and mast cells are distributed throughout the airways. Thus topical delivery of drug for the management of asthma requires an even spread throughout the lungs. Particles of 2-5 microm in diameter have the greatest potential to be deposited throughout the lungs during inhalation, by impaction and sedimentation. Inhaled products, therefore, are formulated such that almost half of the dose emitted during inhalation contains particles less than 5 microm in diameter. This is known as the fine-particle dose. Studies in adults (volunteers and asthmatic patients), using radiolabeling techniques, have shown that although the amount of drug deposited in the airways (total lung dose) from different inhaled products varies, the percentages of this amount distributed throughout the central, intermediate, and peripheral zones are fairly consistent. All that varies, therefore, is the density of the spread. Studies in children indicate that lung deposition is lower than in adults. Nevertheless, all factors which affect lung deposition in adults do so also in children. The lower lung deposition in children indicates the use of adult doses, and the importance of inhaler device and of inhalation technique. The even distribution of inhaled drug throughout the required therapeutic areas highlights the importance of the total lung dose.