due to poor sales blamed, in part, on
the bulky and inconvenient inhaler.
Initially a setback to innovation in this
sector, the failure of Exubera resulted in other companies reconsidering
similar product developments. However, in June 2014 the U.S. Food and
Drug Administration (FDA) approved
Mannkind’s Afrezza, an inhaled insulin
7 The current market success of
this product appears limited, but may
relate to the need for specific patient
screening and product pricing rather
than the efficacy of, or preferences for,
the inhaled medication.
Exubera’s withdrawal has certainly
not hindered the interest in inhalation
delivery, quite the opposite in fact. In
the last four years, 1,350 active inhalation studies—for new, combination,
and existing products, encompassing
802 different diseases and 105 rare diseases—have been logged with the U.S.
FDA clinical trial register. More than
half of these inhalation studies are for
As previously indicated with the
Exubera inhaled insulin device,
the success of inhaled medications depends on two key considerations: drug
formulation and the inhaler device itself.
Innovations in both these aspects of design are leading to more effective drugs—
new, combination, and generic—although
improved powder formulations may be
developed more cost-effectively than new,
A considerable amount of development
time, effort, and money goes into the
production of any inhalation device as
it can contribute to the drug’s success,
irrespective of how effective and benefi-
cial the drug may be to the patient. In-
halation delivery offers something that
is unique compared to other routes of
administration. When used in combina-
tion, it provides extended patent protec-
tion. In the U.S., for example, GSK’s Ad-
vair (seretide) came off patent in 2010,
although the Diskus delivery device
remained in patent through 2016.10 To
be effective, an inhalation device must
be matched to the patient, easy to use,
forgiving of poor technique, and able to
provide feedback to the user about dose
emission and technique (see Table 1).
The size of the market for respiratory
inhaler devices continues to expand, with
estimates suggesting it will reach $43 billion by the end 2025—a compound annual growth (CAGR) of 4.3%.
Formulations for inhalation
Traditionally, the fine drug particles required for delivery in dry powder inhaler
(DPI) devices have been produced by mechanical micronization using air jet mills.
These fine particles are then often com-
bined with a lactose carrier to improve
drug stability and dose control, depending
on the drug type or compound class. More
recently, however, particle engineering
techniques look poised to transform fu-
ture drug formulations (see Box 1).
new techniques have the potential to
provide a more efficacious drug, allowing
lower doses to be used and reducing the
potential for side effects.
Nanotechnology needs special mention. Clearly the size of the particle is
pivotal for inhalation studies in ensuring effective lung deposition. However,
nano-sized materials are broadening the
options for development. Nanomaterials are defined as particles that have one
or more external dimensions 1– 100 nm
The market for nanotechnology usage
in medicine is huge, with applications in
diagnosis, prevention, and treatment.
is predicted that by 2021, the nanotech-nology-enabled drug delivery market will