Currently available dry powder inhalers (DPIs) for drug delivery to the lungs require
turbulent energy to generate and disperse aerosol particles in the respirable range ¿5¿m
during inhalation. The patient's inspiratory effort together with the resistance inside the
device creates this energy. Different inhalers provide varying degrees of resistance to
inhalation flow and require different inhalation techniques for the generation and delivery of
drug fine particles in respirable size range to the lungs.
The aim of this research programme was to identify the influence of inhalation flow,
inhalation volume and the number of inhalations per dose on the ex-vivo dose emission and
the in-vitro aerodynamic dose emission characteristics of the salbutamol Accuhaler®,
Easyhaler®, and Clickhaler® and the terbutaline Turbuhaler® DPIs.
A high-performance liquid chromatography method for the assay of salbutamol sulphate and
terbutaline sulphate in aqueous samples was modified and accordingly validated. In-vitro
dose emission of the four different DPIs was measured using the pharmacopoeia method
with modifications to simulate varying inhalation flows within patient and between patients.
The ranges of the total emitted dose (% nominal dose) at the inhalation flow range of 10 - 60
Lmin-1, following one and two inhalations per metered dose for 2L and 4L inhaled volumes
were as follows: the Accuhaler (52.64- 85.11; 61.88-85.11 and 59.23-85.11; 62.81-85.11);
the Easyhaler (68.35-91.99; 79.94-91.99 and 73.83-92.51; 80.40-92.51); the Clickhaler
(46.55-96.49; 51.12-96.49 and 51.18-101.39; 59.71-101.39) as well as the Turbuhaler
(46.08-88.13; 51.95-88.13 and 48.05-89.22; 48.64-89.22). The results highlight that the four
inhalers have flow-dependent dose emission property to a varying degree using 2L and 4 L
inhaled volumes. There was no significant difference in the total emitted dose between a 2L
inhaled volume and a 4L inhaled volume at each inhalation flow. Furthermore, the total
emitted dose from the Easyhaler®, Clickhaler®, and Turbuhaler® was significantly
(p¿0.001) greater with two inhalations than one inhalation per metered dose across the range
of inhalation flow (10 ¿ 60) Lmin-1. This effect was only observed at inhalation flow less
than 30 Lmin-1 with the Accuhaler®. Overall there is a significant difference in the total
emitted dose.
The ex-vivo dose emission of the four different DPIs has been determined using the In-
Check Dial device to train twelve non-smoking healthy adult volunteers to inhale at slow
(30 Lmin-1) and fast (60 L min-1) inhalation flows through the device with its dial set
corresponding to each inhaler. Subsequently each volunteer inhaled at the trained inhalation
flows through each active inhaler. The local ethics committee approval was obtained prior to
the study and all volunteers gave signed informed consent. The results obtained demonstrate
that the studied inhalers have flow-dependent dose emission, thereby enhancing confidence
in the use of the In-Check Dial® to identify a patient¿s inhalation flows through a variety of
DPIs. Also the total emitted dose determined by ex-vivo methodology was significantly
(p¿0.05) greater with two inhalations than one inhalation per metered dose.
The results of the in-vitro aerodynamic dose emission characteristics highlight that the fine
particle dose (FPD) from the four studied inhalers is flow dependent. Also the minimum
inhalation flow to generate the (FPD) with the appropriate characteristics for lung deposition
has been identified to be 20 L min-1 for the Accuhaler®, Easyhaler® and Clickhaler®, while
that for the Turbuhaler® is about 30 L min-1. Also the inhalation volume above 2L and the
number of inhalations for each dose have respectively no significant (p¿0.05) influence on
the FPD emitted from the four studied inhalers. The results support the present instructions
to patients using these inhalers to inhale once for each dose as fast as they can.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/4861 |
| Date | January 2009 |
| Creators | Ibn Yakubu, Sani |
| Contributors | Chrystyn, Henry, Assi, Khaled H. |
| Publisher | University of Bradford, Institute of Pharmaceutical Innovation |
| 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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