Environmental Engineering Reference
In-Depth Information
allowing adhesion to the carrier until inhalation energy frees the particles. Similar to drug particles
alone, the size, shape, and surface of the carrier particles affect the dispersion. Ternary components
such as L-Leucine and ine particle lactose have been added to blended formulation systems to
decrease binding during inhalation, thus increasing FPF. 81,82 Another approach to increasing FPF
of formulation is to produce large, low-density particles. 83 These particles have aerodynamic diam-
eters in the appropriate range, but the adhesive forces are smaller in ratio because of the large size.
Recent work has evaluated the possibility of delivering liposomes via DPIs. 84,85 β-glucuronidase
was used in one study as a model protein inside dimyristoyl phosphatylcholine and cholesterol
liposomes, which were lyophilized, micronized, and then aerosolized. These showed promise, but
only 15% of the aerosolized particles were below 6.4 μm, and, thus, these formulations require
more optimization. 86 A second study indicated that budesonide could be entrapped inside egg phos-
phatidyl choline and cholesterol liposomes, freeze dried, and then aerosolized. Long shelf life was
demonstrated, along with similar respirable fractions (RFs). 84
1.3.2.1  Passive
Formulation is only one side of the DPI. Even the best formulation needs a vehicle for dispersion, the
inhaler device. The irst DPIs developed used the patient's own inhalation airlow directed through
or across a capsule that is broken prior to inhalation to aerosolize the powder. 5 Because the only
energy source used to deaggregate the particles is the inhalation, these devices are deemed passive
inhalers. To increase the deaggregation energy, bafles or delected airlow are used to create turbu-
lence around the powder bed during inhalation. 76 The irst passive inhalers, like the Spinhaler and
Rotahaler, required loading of a new capsule for each use as single-dose inhalers. Since then multi-
single-dose (device holds multiple capsules or blisters) and true multidose inhalers (dose taken from
reservoir for each inhalation) have become available. Table 1.2 contains a list of some inhalers and
their properties.
1.3.2.2  Active
Using the inspiratory force of the patient is no longer the only way that powder in dispersed in
inhaler design. There has been a recent push to develop active rather than passive inhalers. The
inhalation low rate and force developed vary from breath to breath and certainly from person to
person. This makes it very dificult to both insure that a proper dose is delivered and that the inhaler
is operating at maximum eficiency. Active DPIs use a source of energy other than inhalation to
disperse the powder. Compressed air from a user-operated pump is used as the dispersion energy in
the Inhance™ (Inhale, San Carlos, CA) inhaler. Other patents have been iled for active DPI designs
using energy sources such as vacuum pressure, an impaction hammer, and vibration. 5,87-90
1.3.3  n ebulizers
Nebulization is probably the oldest means of administering drugs to the lungs as aerosols. Because
coordination between breathing and aerosol generation is not necessary, nebulization of therapeutic
agents is mostly used by children, elderly patients, in hospital settings, and for the treatment of lung
diseases such as cystic ibrosis and asthma. 91-93 Adaptive aerosol delivery (AAD) systems, such as
the I-neb, are able to deliver aerosols at different time points during inhalation, such as the tidal
breathing mode (TBM) or the target inhalation mode (TIM), which may provide better delivery
compared to conventional nebulizers. 94-96
Nebulizers produce small polydisperse droplets capable of delivering therapeutic agents to the
deep lung in large doses and can deliver a dose 10 times larger than that of DPIs or MDIs. 91 Mass
median diameters of droplets generated by nebulizers normally range from 2 to 5 μm and have
been used to deliver solutions and suspensions of a great variety of therapeutic agents including
macromolecules and biotechnology products. 97 Miniaturization of the hardware and introduction
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