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Are there differences in throat deposition using variable valved holding chambers?
L. Bakuridze1, S. Neckermann2, V. Andrieu1, J.C. Dubus3
1Laboratoire de Pharmacie Galénique, Faculté de Pharmacie, 27 bd J. Moulin 13385 Marseille cedex 5 France; 2PARI GmbH, 82319 Starnberg, Germany
Service de médecine infantile, CHU Timone-Enfants, 13385 Marseille Cedex 5, France
contact: [email protected]
Valved holding chambers (VHC) assist patients in their “hand- Uniformity of Dose Delivery
Throat deposition
breathing coordination” by providing a reservoir. Moreover, due to The uniformity of dose delivery was characterized by a dose unit As shown in Fig. 2, all tested VHCs reduce oropharyngeal deposition of the retention of large aerosol particles, VHCs can effectively reduce sampling apparatus according to Ph. Eur. based on 10 puffs Flutide® fluticasone compared with the MDI alone (78 µg). Among the non- throat deposition and therefore topical side effects of steroids. HFA MDI and fired from 3 canisters, each. electrostatic VHCs, throat deposition for VORTEX® was significantly Non-electrostatic-VHCs additionally feature beneficial effects, e.g.: It could be shown that the delivery of the three tested MDIs varies more than 4-fold lower in comparison to Nebuchamber® (2.1 vs. 8.7°µg) only in a range of +/- 6 µg from the mean value (Data not shown). and more than 2-fold in comparison to AC Max® (2.1 vs. 4.4°µg). This an increase in delivery of small particles by reducing undesired effect may be due to the cyclone-twist principle of the VORTEX® which drug loss to the inner surface of the chamber Mass Median Aerodynamic Diameter (MMAD)
may help in the retention of large aerosolized drug particles.
an improved dose consistency even with variations in delay The MMAD of the aerosol emitted from the fluticasone-MDI alone and The very efficient reduction in throat deposition by the Babyhaler® (0.22 from the VHCs (except Babyhaler®) is in a range of about 3 µm. The µg) is associated with a more than 3-fold reduction in FPD (13°µg; see In addition the metal non-electrostatic VORTEX® (PARI) with its remarkably lower MMAD obtained from the Babyhaler® is probably figure 1) leading to a possibly suboptimal therapeutic dose.
inspiratory cyclone twist principle could improve the aerosol deli- attributed to its large volume (350°ml) leading to an increased very for patients by improving the clearance of the chamber. adhesion of drug particles to the inner surface of the tube. Aim of the study
MDI alone Nebuchamber®
AC Plus®
MMAD 3.15 ± 0.46 2.99 ± 0.17 3.03 ± 0.17 3.12 ± 0.18 3.06 ± 0.26 2.43 ± 0.45
Most studies about VHCs primarily focus on determining the Fine Particle Dose (FPD) of a specific MDI and VHC combination and disregard measurement of the throat deposition. Table 2: MMAD of the MDI alone and in association with the five VHCs
Therefore the aim of our study was to examine both the FPD and dose [µg]
dose [µg]
the throat deposition for non-electrostatic VHCs in comparison to Fine Particle Dose (FPD)
Fig. 1 shows the FPDs (particles < 4.7°µm) for the five VHCs and the Materials and Methods
MDI alone. It can be seen that the group of the three non-electrostatic VHCs deliver similar FPD, ranging from 48°µg (VORTEX®) up to 5 puffs of a HFA-fluticasone MDI (Flutide® 125 µg, GSK) were 54°µg (Nebuchamber®) without significant differences within this fired at 1 minute interval via a distinct VHC into an Anderson 8- stage impactor in accordance with European Pharmacopoeia The two electrostatic VHCs, AC Plus® (34°µg) and especially Baby- (Ph. Eur.) at 28.3°l/min (28.2 ± 2.1°C and 53.3 ± 7% relative haler® (13 µg), show a significant loss in FPD. This means that on humidity). The USP induction port (throat) and each stage of the average the group of non-electrostatic VHCs delivers 46% and 161% Figure°2: Throat deposition of the MDI alone (A) and with five VHCs (B)
impactor were eluted and an aliquot was assayed by HPLC and higher FPD in comparison to AC Plus® and Babyhaler®, respectively.
Tests were carried out 3 times with 3 VHCs each Statistical analysis was done by ANOVA and t-test (p < 0.05) Although the Babyhaler® reduces throat deposition, it can be assumed Name / Manufacturer
Volume / Material
that the very low FPD bears a potential risk of under dosing electrostatic
AeroChamber® Plus (AC Plus)
The high throat deposition of the Nebuchamber® negates a primary Figure°1: The group
advantage of VHC use: reduction of oropharyngeal deposition and dose [µg]
AeroChamber® Max (AC Max)
of non-electrostatic
VHCs deliver signi-
ficantly the highest

Since VORTEX® is very effective in reducing throat deposition Babyhaler® / GSK
FPD in comparison
combined with a high FPD of fluticasone, VORTEX® may improve Nebuchamber® / AstraZeneca
to AC Plus and the
Fine particle
< 4.7 µm)
Table 1: Main characteristics of the five VHCs used in this study
European Respiratory Society Annual Congress 2006, September 2-6, Munich, Germany


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