Distribution of inhaled aerosols

Marked ethnic differences in infant mortahty and respiratory morbidity have been reported (130). Prematnrely dehvered Afro-Caribbean infants are less likely to develop the respiratory distress syndrome (RDS) than white infants of similar gestational age (131), which snggests that the respiratory system is either more matnre or that airway function is enhanced in black preterm infants (132). Some of these differences may be attributed to differences in nasal anatomy, since the lower total airway resistance found in Afro-Caribbean infants when compared with Caucasian infants of similar age and weight (101) was accounted for by their lower nasal resistance (23). Such differences would be expected to influence both breathing patterns and the distribution of inhaled aerosols. 

Inhalation Administration Aerosol particles of drug can be inhaled into the lungs. Because of the large surface area of the alveoli, absorption is rapid and effective. As the lungs are richly supplied with capillaries, distribution of inhalational drugs is very quick (refer to Exhibit 4.14 on inhalable insulin). 

Figure 2 Coronal slices and projection view obtained after inhaling a 1.5 pm aerosol of F1Xj from the Ultravent jet nebulizer (Mallinckrodt, St. Louis, MO). Slices are shown from the anterior, midsection, and posterior lung for a normal subject (right) and a subject with cystic fihrosis (left). Greater detail of lung distribution of the aerosol is provided by the PET scan. The cumulative or projection scan (all the coronal slices summed) would be comparable visually to 2D images obtained with a gamma camera.

Newman SP, Pellow PGD, Clarke SW. Droplet size distributions of nebulised aerosols for inhalation therapy. Phys Physiol Meas 1986 7 139-146. 

The two main determinants for medicine deposition in the respiratory tract are the aerodynamic size distribution of the aerosol and the manoeuvre with which the aerosol is inhaled. They govern the mechanisms that are respraisible for particle deposition in the lungs. By varying the inhalation manoeuvre, not only the distribution in the airways for the same aerosol is changed in many cases also the amount and properties of the delivered fine particle dose are affected. The complex interplay between inhalation manoeuvre, aerosol properties and site of deposition has led to many misconceptions regarding the best inhaler choice for individual patients and the way these inhalers need to be operated to achieve optimal therapy for the patient. In this chapter the medicine deposition mechanisms for inhaled aerosols are explained as functions of the variables involved. In addition, the working principles of different inhaler types are described and it is discussed how their performance depends on many inhalation variables. Finally, some persistent misconceptions in the literature about the most preferable dry powder inhaler properties and performance are umaveUed. 

MMAD is frequently presented as the parameter characterising aerosols from inhalation devices best. This is not true however. To judge the quality of a therapeutic aerosol from a particular type of inhaler, more information is needed. The MMAD does not give any information about the size distribution of the aerosol particles. Substantial mass fractions may be outside the desired size range for adequate deposition of active substance in the target area, even when MMAD looks very favourable. Moreover, MMAD does not give information about the mass fraction of the dose (label claim) that has been delivered within the desired size range. For aU types of inhalers, the delivered fine particle dose (FPD) is much lower than the label claim and this may vary from 10 % to 60 % for DPIs and up to 90 % for... 

The fate of an orally inhaled particle is strongly dependent on its aerodynamic diameter. Generally, particles larger than ca. 5 pm will inertially impact the mouth or throat, and be swallowed. Particles in the range of ca. 3-5 pm in diameter will reach the upper or conducting airways of the lung and can deposit on the smooth muscle of these structures. Particles of approximately 1-3pm may follow the airstream all the way to the alveoli and be deposited, and particles less than about 1 pm may be exhaled. Thus, careful control of the particle size distribution of medical aerosols is essential for effective drug delivery. 

For radionuclides inhaled by workers in particulate form, it is assumed that entry into and regional deposition in the respiratory tract are governed only by the size distribution of the aerosol particles. The situation is different for gases and vapours, for which respiratory tract deposition is material specific. Almost all inhaled... 

Swift DL. Use of mathematical aerosol deposition models in predicting the distribution of inhaled therapeutic aerosols. In Hickey A, ed. Inhalation Aerosols Physical and Biological Basis for Therapy. New York Marcel Dekker, 1996 51-81. 

Fig. 1. Deposition of inhaled particles of different sizes (mass median aerodynamic diameters) in the three regions of the respiratory tract. Each shaded area indicates the variability of deposition when the aerosol distribution parameter, o, (geometric standard deviation) was varied from 1.2 to 4.5. The assumed tidal volume was 1450 cm3. (Reproduced from Health Physics, vol. 12, pp. 173-207,1966 by permission of the Health Physics Society).

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