TAILORING DRY POWDER INHALER PERFORMANCE BY - RCPE

766 Maas et al.
of the cartridge was filled with powder. Each metered
mass was determined by weighing the inhaler before and
after the discharge.
2.8 Delivered Dose
The delivered dose was determined by discharging 10
doses from the Novolizer multidose inhaler using the
experimental setup described in the European Pharmacopoeia
(Ph. Eur., 2008b). Eighty percent of the volume
of the cartridge was filled with powder. In contrast
to Pharmacopoeia, 10 subsequent doses were examined,
each consisting of five puffs in order to ensure the
proper quantification of the drug. The unit sampling apparatus
was rinsed with 100.0 mL of diluted acidic acid
(pH 3), which then was transferred into an Erlenmeyer
flask together with the filter and ultrasonically treated
(5 min) in order to dissolve the drug potentially present
on the filter. The amount of active was determined by
HPLC.
2.9 Assessment of Fine Particles
The aerodynamic assessment of fine particles (Ph. Eur.,
2008c) was performed using the Apparatus E (NGI, Copley
Scientific, UK-Nottingham). The following preparation
steps were necessary. The small cups of the NGI
were coated with 2 mL coating agent (solution of 5% of
a mixture of glycerol and polyoxyethylene-20-cetylether
(95:5) in isopropanol), the large cups with 4 mL. The preseparator
was filled with 15 mL of diluted acetic acid.
The measurements were performed using 79.3 L/min
flow rate. The flow rate was measured with an electronic
digital flowmeter (Model DFM, Copley Scientific, UK-
Nottingham). Pumps (Typ SHC P3, Typ HC P3) and
the critical flow controller (Model TPK) were also from
Copley Scientific. The ordered mixture was filled in the
powder container of a Novolizer (filling grade 80%),
which was fixed to the throat of the impactor by a suitable
adapter. Fifty doses were discharged into the impactor.
The dose of active ingredient on the stages was
dissolved in 20.0 mL of diluted acidic acid by gently
shaking. The preseparator was rinsed with 50.0 mL of
diluted acidic acid (pH 3) and diluted at the ratio 1:5.
The drug was determined by HPLC. The fine particle
dose is calculated as the dose of active ingredient exhibiting
an aerodynamic diameter of