Delivery of Inhaled Medications

Ariel Berlinski, MD, FAAP

Introduction

•Aerosol therapy is administered to infants and children to treat many respiratory conditions (according to Food and Drug Administration– approved indications and off-label indications).

•Advantages of inhaled medications include

—Providing topical action

—Allowing drugs to begin working faster

—Achieving high in situ drug concentration

—Allowing the use of lower doses, thus decreasing the risk for side effects

•Upper-airway and intrapulmonary delivery is used for

—Asthma (corticosteroids, long- and short-acting bronchodilators)

—Cystic fibrosis (corticosteroids, long- and short-acting bronchodilators, antibiotics, hypertonic saline, dornase alfa)

—Croup (epinephrine and corticosteroids)

—Chronic lung disease of prematurity (corticosteroids, long- and short-acting bronchodilators)

—Pulmonary hypertension (vasodilators)

—Chronic airway infection associated with non–cystic fibrosis bronchiectasis

•Systemic delivery is used for

—Diabetes (insulin)

—Pain (opioids)

Types of Delivery Devices

•There are 3 main types of aerosol delivery devices.

—Nebulizers

—Metered-dose inhalers (MDIs)

▪Pressurized MDIs (pMDIs)

▪Soft mist

—Dry-powder inhalers (DPIs)

•The advantages and disadvantages associated with each type of device are outlined in Chapters 106, 107, and 108.

Definitions

•Aerosols are a suspension of liquid (nebulizer and MDIs) or solid particles (DPIs) in a carrier gas.

•Aerosols are typically characterized by 3 different parameters.

—A central tendency measurement known as mass median aerodynamic diameter (MMAD) represents the particle diameter that has half of the drug mass below and above its size.

—For the dispersion measurement known as geometric standard deviation (GSD):

▪Most medical aerosols are polydisperse.

▪An aerosol with a GSD <1.2 is considered monodispersed.

—The respirable fraction is the proportion of aerosol that lies between 1- and 5-µm diameter.

▪This particle size range is considered highly likely to be deposited in the lungs.

▪Some investigators suggest that using aerosols with smaller MMAD could enhance drug deposition in infants and young children.

▪It is not clear if this aerosol size is ideal for drug delivery through artificial airways (ie, tracheostomy).

Mechanisms of Aerosol Deposition

The process of aerosol deposition is mainly governed by 3 mechanisms.

Inertial Impaction

•This occurs when sudden changes in the direction of the flow take place.

•Fast-traveling aerosols, as well as those with large particle size (MMAD between 3 and 5 µm), deposit via this mechanism.

•It occurs mainly in the upper and large airways.

•Inhaling aerosols at a lower inspiratory flow rate will enhance intrapulmonary deposition.

Gravitational Sedimentation

•This is the main deposition mechanism for particles with an MMAD in the 0.5–3.0-µm range.

•The longer the residence time of the particles, the more likely that gravitational forces will determine deposition. This is why a breath- holding maneuver increases intrapulmonary deposition.

Brownian Diffusion

•Deposition occurs by random particle motion at the alveolar level.

•This is the main deposition mechanism for particles with an MMAD smaller than 0.5 µm. Many of these small particles are exhaled.