The present work aimed at assessing the dose emission and aerodynamic particle size characteristics
of formoterol fumarate from Atimos Modullite, a metered dose inhaler (MDI) and Foradil Aeroliser,
Easyhaler, and Oxis Turbuhaler dry powder inhalers (DPI) at different inhalation flow rates and
volumes using in vitro methodology. Recognised methods have been adopted and validated to
generate the results.
The in vitro characteristics of formoterol were measured according to standard pharmacopeial
methodology with adaptation to simulate routine patient use. The dose emission from the Atimos
Modulite was determined using inhalation volumes of 4 and 2 L and inhalation flows of 10, 28.3, 60,
and 90 L/min. The %nominal dose emitted was consistent between the various flow rates and
inhalation volumes of 4 and 2L. The particle size distribution was measured using an Anderson
Cascade Impactor (ACI) combined with a mixing inlet valve to measure particle size distribution at
inhalation flow rates below 30 L/min. The particle size distribution of formoterol from Atimos
Modulite was measured using inhalation flows of 15, 28.3, 50, and 60 L/min with and without
different spacers, Aerochamber and Volumatic. The mean fine particle dose (%nominal dose)
through an Atimos without spacer were 53.52% (2.51), 54.1% (0.79), 53.37% (0.81), 50.43% (1.92)
compared to Aerochamber 63.62% (0.44), 63.86% (0.72), 64.72% (0.47), 59.96% (1.97) and
Volumatic 62.40% (0.28),63.41% (0.52), 64.71% (0.61), 58.43% (0.73), respectively. A small
decrease in the fine particle dose was observed as the inhalation flow increased, but this was not
significant. The respective mean mass aerodynamic diameter (MMAD) increased as the flow rate
was increased from 15 of 60 L/min. Results also suggests that the use of spacers provides better lung
deposition for patients with problems using MDI.
The dose emission from the Foradil Aeroliser was determined using inhalation volumes of 4 and 2 L,
at inhalation flows of 10, 15, 20, 28.3, 60, and 90 L/min plus two inhalations per single dose. The
%nominal dose emitted using 2 L inhalation volume was approximately half when compared to
results obtained using inhalation volume of 4 L. A significantly (p<0.001) higher amount of drug
was also emitted from Easyhaler® at inhalation volume of 4 L through flow rates of 10, 20, 28.3, 40,
and 60 L/min compared 2 L. Similar results were observed through Oxis Turbuhaler at inhalation
flow rates of 10, 20, 28.3, 40, and 60 L/min.
Comparative studies were also carried out to evaluate the particle size distribution of formoterol
through the DPIs. The nominal fine particle dose through Aeroliser using inhalation flows of 10, 20,
28.3, 60 and 90 L/min were 9.23%, 14.70 %, 21.37%, 28.93%, and 39.70% for the 4 L and 4.17%,
5.55%, 7.28%, 8.41%, and 11.08% for the 2 L, respectively. The respective MMAD significantly
(p<0.001) decreased with increasing flow rates. Aeroliser performance showed significant (p<0.001)
increase in the % nominal fine particle dose for two inhalations compared to one inhalation at both 4
and 2 L.
The Easyhaler was measured using inhalation flows of 10, 20, 28.3, 40, 60 L/min. The nominal fine
particle dose were 19.03%, 27.09%, 36.89%, 49.71% and 49.25% for the 4 L and 9.14%, 15.44%,
21.02%, 29.41%, 29.14% for the 2 L, respectively. The respective MMAD significantly (p<0.001)
decreased with increasing flow rates. Easyhaler performance at both 4 and 2 L showed no significant
differences between one and two inhalations at low flow rates (10, 20, 28.3), but this was significant
(p<0.05) at higher flow rates (40 and 60 L/min).
The Oxis Turbuhaler was also measured using inhalation flows of 10, 20, 28.3, 40, 60 L/min. The
nominal fine particle dose were 12.87%, 24.51%, 28.25%, 34.61%, 40.53% for the 4 L and 8.55%,
15.31%, 21.36%, 19.53%, 22.31% for the 2 L, respectively. Turbuhaler performance showed
significant (p<0.05) differences between one and two inhalations at varying flow rates 2 L inhalation
volumes, but not at 4 L.
The use of Foradil Aeroliser delivers small particles as the Oxis Turbuhaler using two inhalations
hence delivering formoterol deep into the lungs. Also, this thesis shows that high flow resistance of
Turbuhaler will indeed influence the ability of patients with severe asthma or children to use the
system. Beside, Easyhaler produced the highest drug delivery to the lungs, thus, making it a more
desirable system to use, especially for children and asthma sufferers.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/5686 |
| Date | January 2011 |
| Creators | Alaboud, S. |
| Contributors | Assi, Khaled H., Chrystyn, Henry |
| Publisher | University of Bradford, School of Pharmacy |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Thesis, doctoral, PhD |
| Rights | <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>. |
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