Pharmaceutical Manufacturing Handbook: Production and

704 AEROSOL DRUG DELIVERY
Transparent
chamber
TransJector
(disperser)
Blister
pack
Pump
handle
Actuation
button
FIGURE 5 Exubera Inhaler. (Reprinted from ref. 175 . Courtesy of Mary Ann Liebert,
Inc.)
of fl ow rate independence [214, 217 – 221] . When choosing a DPI, the effect of inhalation
fl ow rate should be assessed on a case - by - case basis for each individual DPI,
and readers should be aware of contradictory studies, especially when comparing in
vitro and clinical performance. The Turbuhaler is one such example, where some in
vitro studies show high variability; however, this is not refl ected in clinical studies
[215, 220, 222] .
From these and many other studies it can be concluded that a desirable characteristic
for any DPI is that its dose delivery performance is independent of inhalation
fl ow rate. A second generation of DPIs have been developed that incorporate
a combination of improved powder formulations, more effective turbulent dispersion
within the inhaler, and in some cases an active dispersion mechanism. The
Exubera inhaler releases a bolus of compressed air through the formulation and
actively generates an aerosol cloud from the powder (Figure 5 ). The cloud is held
within a reservoir chamber from which the patient then inhales the insulin dose
[175] . Active dispersion improves device aerosolization effi ciency, with greater than
50% of the dose being deposited in the lungs, while minimizing the reliance on the
patients ’ inspiratory effort.
Single - and Multiple - Dose DPI s Inhalation powder dose metering is one of the
problems encountered by DPI formulators. The powder dose can range from 250 μ g
in the drug - only Pulmicort Turbuhaler formulation to 25 mg in the lactose - blended