Opportunities For Control Of Deposition And Targeting

Except in situations when an aerosol is deliberately targeted for deposition in the mouth or in the nose, the material landing in these regions has no useful purpose for the therapy of respiratory diseases. Therefore, minimizing the extrathoracic deposition of inhalation aerosols is usually a desirable design feature of these delivery systems. Although there are many studies providing the evidence that inhalation therapy is improved by shifting the deposition from the oropharyngeal to the pulmonary region, data that would show that a more selective targeting within the latter region is desirable are rather scarce. The advantages of delivering pentamidine aerosols selectively to the lung periphery is the clearest case, because the receptors, the infecting microorganisms, reside in the alveolated parts [21]. Bronchodilator drugs contained in particles or droplets with smaller mass median aerodynamic diameters achieve a more potent therapeutic effect than the coarser aerosols [76,77], but how this is affected by changes in the regional deposition is not known. Similar results of improved efficacy with smaller particles were obtained with the prophylactic drug cromolyn sodium [78]; in this case, however, the less effective particles tested had a mass median aerodynamic diameter so large (11 mm) that they would have deposited almost entirely in the oropharynx.

Particle Velocity and Flow Rate

The deposition in the mouth is largely due to impaction (except for ultrafine aerosols). This mode of deposition therefore increases with particle size and velocity. The reduction of oropharyngeal deposition is desirable both to improve the efficiency of lung deposition and to reduce its variability [26]. To accomplish this, the velocity of the particles must be sufficiently low. The lower bound for the particle velocity is dictated by the inspiratory flow carrying the aerosol cloud. But some aerosol generators impart high velocity to the particles in the course of formation of the aerosol cloud.

In particular, the propellant-driven metered-dose inhalers release the aerosol cloud at the very high velocity caused by the pressure of the propellant. The open-mouth technique of inhalation [79] helps to slow down the droplets (and to evaporate the volatile excipients). An even more effective solution is to use spacer devices [4,79-87], in which the aerosol cloud can slowed down, the volatile constituents can evaporate, and any large particles will sediment out. Moreover, the patient can then inhale the remaining aerosol under optimal conditions for pulmonary delivery [4,8,56,79], that is, with a slow inspiratory flow rate.

With breath-driven dry powder inhalers, as with nebulizers, the aerosol cloud is inhaled at the inspiratory flow rate. However, experimental evidence from both in vitro [88] and in vivo studies [15,30] indicates that at least some of these inhalers require high inspiratory flow rates to achieve adequate deaggregation of the drug power. The higher the flow, the more energy is available to emit the dose from the device and disperse the particles; however, this is accompanied by higher inertial impaction. To avoid the dependence on the patient's inspiratory effort and the negative impact of high inspiratory flow rate on lung deposition, "active" dry powder inhalers have evolved that use other forms of energy (e.g., compressed air) to disperse the powder [89].

For aerosols in which the particle velocity is determined by the inspiratory flow rate and the particle size is not sensitive to it, it is expected that the increase in flow rate increases the upper and central airway deposition. For example, Ryan et al. [90] found that fast vital capacity inhalation resulted in a greater proportion of nebulizer aerosol depositing in the central airways than when the aerosol was inhaled slowly. However, the dependence on the inspiratory flow rate becomes more subtle when the particles have intrinsic velocity (such as droplets generated by propellant-driven metered-dose inhalers that need to be entrained into the inhaled air) or the particle size is inspiratory flow dependent (as in the case of passive dry powder inhalers).

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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