Physical Causes of APSD Changes in Aerosols from OIPs and Their Impact on CI Measurements - Good Cascade Impactor Practices, AIM and EDA for Orally Inhaled Products - page 57

The provision of a patient-independent source of energy to disperse the powder, as
takes place within an active DPI, is one way to address this limitation [ 6 ]. There is
more variety in the design of different DPIs than associated with the other OIP
classes, and this diversity may have implications when attempting to connect the
patient interface of the inhaler to the CI system.
At the outset, it is important to realize that all of the changes influencing particle
size of OIP-generated aerosols that have just been outlined affect the entire APSD.
That is, they are not particularly size-selective. It follows that there are no processes
which would selectively make the mass of API collecting on one stage of a CI grow
and that on its neighboring stage decrease, without a concomitant change in the rest
of the APSD profile.
In 2000, a consensus statement was developed by a group of experts assembled to
evaluate critically each of these forms of aerosol generator [ 9 ]. This statement includes
much useful information concerning the advantages and limitations of each OIP-
based aerosol generator from the perspective of the practicing clinician and based on
currently available medications at the time of publication. Individual papers from
these authors, describing each type of inhaler class can be found in the same issue
(June 2000) of the peer-reviewed journal, Respiratory Care . Although CFC propel-
lants for MDIs have almost entirely been withdrawn from most irst-world markets
since that statement was published, the descriptions of the principles of aerosol gen-
eration provided at this conference still apply to HFA-propellant operated MDIs today.

3.2 Deposition of Aerosols in the Human Respiratory Tract

The human respiratory tract (HRT) has evolved to act as an airborne particle size
classifier to prevent the ingress of inhaled aerosols to the gas-exchange region in the
distal lung [ 11 ]. Thus, moving from the proximal carina to the distal alveolar sacs,
the airways in successive generations steadily decrease in diameter, such that par-
ticles from an incoming aerosol are deposited in size order, beginning with the larg-
est [ 5 ]. The dimensions of the airways enlarge as the result of growth from the fetal
to adult stage [ 12 ]. API delivery by pulmonary inhalation exploits the use of aero-
solized particles which are least efficiently trapped in the upper airways and best
able to reach the conducting airways (for local drug action) or the respiratory air-
ways (for either local action or systemic absorption) [ 13 - 15 ].
The current International Commission on Radiological Protection (ICRP) human
respiratory tract model for radiological protection provides a profile of the likely
deposition fate of incoming aerosol particles based on their aerodynamic size
(Fig. 3.1 ).
These curves are based on a large repository of data associated with radiological
protection and therefore relate to the prevention rather than delivery of particulates
to the HRT.
The aerodynamic diameter size scale ( d ae ), introduced in Chap. 2 , defines most
closely the transport and deposition of particles in the critical size range from about