TAILORING DRY POWDER INHALER PERFORMANCE BY - RCPE

Tailoring Dry Powder Inhaler Performance 769
90 ◦ C, and 8.9 mg for formulations containing mannitol
120 ◦ C.
In addition, the uniformity of dosing was evaluated by
calculating the coefficient of variation of the mass of each
batch (A, B, C). The mean and the standard deviation
of the three coefficients of variation of each formulation
(mannitol 60 ◦ C, 90 ◦ C, 120 ◦ C) were calculated. The coefficients
of variation are given in Fig. 4. Despite the differences
in surface topography, there is no significant difference
between the formulations, the coefficient of variation
showing values of 27.1% for ordered mixtures with
mannitol 60 ◦ C, 36.2% for ordered mixtures with mannitol
90 ◦ C, and 21.3% for ordered mixtures with mannitol
120 ◦ C. Therefore, even if there was a difference of the
flowability of the pure carriers prior to mixing of the carriers
with the active, the attachment of the drug particles to
variation coefficient of the mass / %
50,0
40,0
30,0
20,0
10,0
the carrier surface must have influenced the surface properties
to such an extent that a similar powder flowability
and dosing was finally obtained.
3.4 Delivered Dose
The delivered dose is defined by the dose of active delivered
to the patient by the inhalation device. In this study,
it was determined by discharging 10 doses from the Novolizer
multidose inhaler using the experimental setup described
in the European Pharmacopoeia (Ph. Eur., 2008b).
In contrast to what is described in Pharmacopoeia, 10
subsequent doses were examined, each consisting of five
puffs in order to ensure the proper quantification of the
drug. The dose of active delivered was determined by
HPLC (Fig. 5).
0,0
Mannitol 60°C Mannitol 90°C Mannitol 120°C
FIG. 4: Variation coefficient of the metered mass of 50 single doses of formulations containing mannitol carrier
particles spray dried at 60◦C, 90◦C, and 120◦C; n = 3, mean ± standard deviation.
delivered dose / µg
0
0
0
0 1 2 3 4 5 6 7 8 9 10
number of the dose discharged
FIG. 5: Delivered dose of three batches of each formulation containing mannitol carrier particles spray dried at 60◦C, 90◦C, and 120◦C. Volume 20, Number 9, 2010
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Mannitol
120 °C
Mannitol
90 °C
Mannitol
60 °C