Characteristics influencing the effective administration of drugs as inhalation aerosols.

S tudies of the effective delivery of pharmaceutical inhalation aerosols have hinged on their particlesize characteristics and the mass, or dose, of drug delivered to the lung. Preparation and delivery of aerosols have been approached using these criteria with the intention of optimizing lung deposition. Aerosol particles and droplets exhibit a range of sizes which constitute their distribution. The best statistical fit to this distribution is frequently lognormal.l The expressions used to define particle-size distributions are the mass median aerodynamic diameter and the geometric standard de~iation.~, ' The general characteristics of an aerosol that result in appropriate lung deposition and therapeutic effect have been known for some time. Particles with a median diameter up to 5 pm will be deposited predominantly in the lungs3 Such particles are considered respirable, and the term "respirable fraction" has been used to describe the proportion of the total distribution in this approximate size range. A narrow distribution will result in higher deposition in the periphery, while a broad distributio~~ will result in increased central and upper airway deposition.' The development of pressurized metered dose inhalers (MDIs) for the administration of aerosols was a major advance in drug therapy. The efficiency of these devices has been subject to scrutiny. Despite their delivery of a therapeutically effective dose, this constitutes a small proportion of the total dose delivered by the d e v i ~ e . ~ . p W Efforts have been directed to increase efficiency or eliminate redundancy of the devices. Particles generated by an MDI are most significantly influenced by inertial and sedimentary mechanisms of deposition. These are subject to kinetic factors related to velocity and evaporation of droplets following g e n e r a t i ~ n . ~ , ~ ~ ~ The distance and direction traveled by each of the droplets prior to entry into the lung will influence the particle-size distribution and the dose delivered. It has been shown that deposition in the oropharynx may be reduced by administering aerosols through spacer devices6 When aerosols are delivered by other methods, the influence of the administration accessories upon particle size and dose delivery must be considered. The issue of delivery of aerosols to mechanically ventilated patients has been considered.'," Aerosols are administered via endotracheal tubing for this p t ~ r p o s e . ~ . ~ ~ ~ In this issue of Chest, Taylor et al (see page 920) have considered the effect of using intraluminal catheters (ILCs) to deliver aerosols through endotracheal tubes. They have studied the effect of ILCs as a function of diameter and length upon the delivery of salbutamol (albuterol) delivered by MDI (Ventolin, 100 pg per puff). Their method involves the in vitro assessment of aerosols exiting a tracheal tube when ILCs of known length and diameter are employed. The authors conclude that the ILCs act as an extension of the actuator nozzle. Thus, a larger respirable fraction of aerosol reaches the end of the tracheal tube through long, narrow ILCs. Optimal dosing, logically, occurs when the catheter extends the full length of the tracheal tube. This is a unique approach to overcoming the problems of deposition of aerosols in the upper respiratory tract or in administration accessories during administration to mechanically ventilated patients. The authors have satisfied the usual criteria for assessment of the efficiency of their system by considering particle size and dose delivery. Anthony ]. Hickey, P h . D. Chicugo