Pharmaceutical Manufacturing Handbook: Production and

5.8.3
THERAPEUTIC INDICATIONS FOR AEROSOL DELIVERY 687
THERAPEUTIC INDICATIONS FOR AEROSOL DELIVERY
5.8.3.1 Current Applications
Aerosolized drug delivery is currently used to deliver a limited range of therapeutic
classes of compounds. These are mainly for asthma and chronic obstructive airway
disease. These classes of compounds include short - and long - acting β - adrenoceptor
agonist, corticosteroids, mast cell stabilizers, and muscarinic antagonists. Of recent
note is the popularity of combination products. These have obvious advantages from
a patient compliance perspective. In addition, certain combinations of drugs have
shown synergistic therapeutics benefi ts when compared to the drugs given by separate
inhalers [45] . Long - acting β - adrenoceptor agonists and corticosteroids formulated
as combination products are available as both MDIs and DPIs [46] . Also
recently introduced was a MDI formulation, the R enantiomer of albuterol, which
is believed to be mainly responsible for bronchodilation in the racemic mixture [47] .
Zanamivir is licensed in the United States as an inhaled antiviral agent for the treatment
of infl uenza [48] . Recombinant human deoxyribonuclease (rhDNAase) is
available as a nebulizer product for the treatment of cystic fi brosis, in which it acts
to liquefy viscous lung secretions [49] . And recently, insulin was approved as an
inhaled powder for glycemic control in type I and II diabetes (see Section 5.8.6.5 )
[50] .
5.8.3.2 Future Applications
Research and development are presently underway covering a vast array of novel
applications. Clark (2004) provides an extensive list of products and their current
state of development [51] . A signifi cant future advance will be the development
of inexpensive, noninvasive, stable, single - dose vaccine delivery via the lungs [52] .
Efforts in this area are being led by the World Health Organization in the Measles
Aerosol Project, and in a separate project, the Grand Challenges in Global Health
initiative has funded a program to further develop an inhalation aerosol measles
vaccine. Delivery of the measles vaccine via the lungs has been demonstrated to
be both safe and effective [53 – 58] . Now the challenge of each of these projects is
to produce stable inhalation vaccine formulations to be delivered via inexpensive
inhalers while maintaining both safety and effi cacy [59] . The use of inhaled
vaccinations in the event of a bioterrorism attack is also a potential application
[60, 61] .
The use of the inhalation route for the delivery of gene therapy is also an area
of signifi cant interest [60, 62] . Cationic liposomes and polymers together with adenoviral
vectors containing the reporting genes have been aerosolized using nebulizers
for the majority of clinical studies. However, there are a signifi cant number of challenges
that must be overcome before pulmonary gene delivery is deemed completely
successful, the most important being low gene transfer effi ciency at the
cellular level. This problem is not unique to inhalation therapy. Inhalation of a
recombinant adenovirus containing the cystic fi brosis transmembrane regulator
(Ad2/CFTR) demonstrated the feasibility of this approach for the treatment of
cystic fi brosis [63, 64] . However, the limited duration of transfection and low cellular
uptake effi ciency still remain a barrier to full utilization of this route [60, 65] . There