Drug Targeting Organ-Specific Strategies

3.9 Inspiratory Pressure and Relevant Flow Parameters 75
where Φ V is the volumetric flow rate, ρ A is the density of the air (upstream of the flow constriction)
and Fu(A) is a function of the cross-section of the flow constriction. Several authors
use a simplification of this formula, written in terms of driving force (√∆P), airflow resistance
(R E) and volumetric airflow (Φ V) (e.g. references [22,100]).
√∆P = R E x Φ V
(3.2a)
In this equation, R E is the reciprocal of Fu(A) x √(2/ρ A). If there is no interaction between
the flow through the inhaler and the flow in the respiratory tract, total resistance (R TOT) may
be written as R TOT 2 = RI 2 + RE 2 . It has been reported that a high external resistance influences
the shape and width of the human pharynx and larynx in a manner favourable for deep
lung deposition [101].
The resistance of dry powder inhalers can be calculated by measuring the volumetric flow
rate and the pressure drop across the device simultaneously and applying Eq. 3.2a for the calculation.
Values for some marketed DPIs are given in Table 3.7, showing that there are remarkable
differences between devices.
Table 3.7. Airflow resistances of some marketed dry powder inhalers in kPa 0.5 min l –1 .
Reference [100] [144] [145] Mean
Glaxo Rotahaler 0.013 0.013 0.014 0.0133
Fisons Spinhaler 0.016 0.015 0.015 0.0153
Pharbita Cyclohalera 0.017 0.018 0.018 0.0177
Sofotec Novolizer – – 0.026 0.0260
Glaxo Diskhalerc 0.021 0.018 0.030 0.0230
Glaxo Diskus – – 0.032 0.0320
Astra Turbuhaler 0.031 0.039 0.040 0.0367
Inhalator Ingelheimb 0.056 0.053 0.048–0.058 0.0540
Chiesi Inhaler – 0.093 – 0.0930
a Also known as ISF inhaler and Novartis (Foradil) Inhaler.
b The range in reference [145] is a consequence of poor reproducibility in capsule piercing.
c The spread for the Glaxo Diskhaler may come from the use of two different devices: four-dose [145]
and eight-dose [100, 144].
1 technical bar equals 1000 mbar = 105 Pa (N m-2 or kg s-2 m-1 ) = 102 kPa
Resistances have been (re-)calculated for standard liters per minute (at 20 °C: LS min-1 =
1,0733*LN min –1 ).
3.9 Inspiratory Pressure and Relevant Flow Parameters
Several authors measured attainable pressure drops as a function of the external resistance
for different groups of volunteers. Healthy male subjects (during maximal inspiration) are
able to create a pressure drop (on average) of 6.7 kPa through an airflow resistance of
0.038 kPa 0.5 min l –1 , (which is in the range of that of marketed DPIs, see Table 3.7), whereas
females are able to create a pressure drop of 3.8 kPa under the same resistance [22]. Differences
between different groups of patients depend on the degree to which pulmonary func-