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Budesonide inhalation suspension delivered
via Ventstream® breath-enhanced jet nebulizer
K. Nikander1, M. Cruz-Rivera2, and G.C. Smaldone3
1
Nikander01.indd/teb/IPC ISAM 2003
Profile Therapeutics plc, Bognor Regis, UK; 2AstraZeneca LP, Wilmington, DE;
3
Pulmonary/Critical Care Medicine, SUNY, Stony Brook, NY
INTRODUCTION
DISCUSSION
Ventstream (Profile Therapeutics) is a breath-enhanced jet nebulizer
which has been shown clinically to be suitable for delivery of nebulized
budesonide.1-2 In vitro studies have shown that the drug mass output, the
droplet size and nebulization time will vary with the nebulizer and compressor system used.3 The amount of drug inhaled (inhaled mass) will also
depend on the patient’s breathing pattern. It is therefore important to characterize the jet nebulizer with the drug to be used in terms of inhaled mass
and droplet size using a test setup that mimics the treatment situation.
In Fig. 2 (modified from ref. 3) the inhaled mass of budesonide for the two
Ventstream nebulizers (bars 8 and 11) has been added to the inhaled mass
of budesonide of 27 other nebulizers. The inhaled mass of budesonide
achieved with the Ventstream nebulizer was comparable to that of the most
efficient previously tested nebulizers. The amount of budesonide in the respirable fractions was, however, clearly larger than the other nebulizers.
Fig 2.
AIM
The aim of the study was to characterize the
Ventstream jet nebulizer - using Passport
(Invacare, OH) and Pulmo-Aide (DeVilbiss, IL)
compressors - in terms of inhaled and exhaled
masses, mass median aerodynamic diameter
(MMAD), and the amount of budesonide in the
respirable fractions ≤6µm and ≤3.5µm.
METHODS
The Ventstream nebulizer was connected via a filter to a Harvard
sinus pump which generated a simulated breathing pattern (VT 200ml,
25 BPM, duty cycle 0.5) through the nebulizer. Each nebulizer was
charged with 1.0 mg budesonide in 2 ml (Pulmicort RespulesTM,
AstraZeneca LP) and run until dryness, using either Passport or Pulmo-Aide
compressors. Five Ventstream nebulizers were used with each compressor. The inhaled and exhaled masses were determined with filters attached
to the nebulizer (Fig. 1a). Droplet size and amount of budesonide in the
respirable fractions were determined through a low flow cascade impactor
connected in line between the nebulizer and the inhaled mass filter (Fig.1b).
The amount of budesonide collected onto the filters was determined using
liquid chromatography.
Fig. 1a.
Nebulizer
Pari LC Jet Plus
Pari LC Jet Plus
Intertech
Baxter Misty Neb
Hudson T Updraft II
Hudson T Updraft II
Ventstream
Compressor
Pulmo-Aide
Pari Master
Pulmo-Aide
Pulmo-Aide
Pulmo-Aide
Hudson
Passport
9
10
11
13
14
15
16
22
Nebulizer
Hudson AVA-NEB
Aiolos
Ventstream
Pari LC Jet
Hudson AVA-NEB
Pari LC Jet
DeVilbiss Pulmo-Neb
DeVilbiss Pulmo-Neb
Compressor
Pulmo-Aide
CR 60
Pulmo-Aide
Pari Master
Hudson
Pulmo-Aide
Pulmo-AideTraveller
Pulmo-Aide
CONCLUSIONS
For budesonide inhalation suspension delivery,
the inhaled mass of the Ventstream jet nebulizer
is comparable to that of other efficient jet
nebulizers.
The respirable fraction of the inhaled mass
of budesonide achieved with Ventstream is,
however, larger.
Fig 1.b
The positive ratio of respirable fraction :
inhaled mass achieved with the Ventstream
nebulizer should in clinical practice minimize
oropharyngeal deposition and increase lung
deposition.
RESULTS
The nebulization times to dryness were 7.3 min for Ventstream/Passport and
9.1 min for Ventstream/Pulmo-Aide. The mean inhaled and exhaled masses
of budesonide, the MMAD and the amount of budesonide in the respirable
fractions are shown in the table below.
Inhaled
mass (sd)
Exhaled
mass (sd)
MMAD
(GSD)
Respirable
fraction
≤ 6 µm
Respirable
fraction
≤ 3.5 µm
Ventstream/Passport
139 µg (14)
38 µg (13)
2.6 µm (2.0)
87 %
68 %
Ventstream/Pulmo-Aide
136 µg (26)
43 µg (10)
2.5 µm (1.8)
91 %
77 %
Nebulizer/compressor
1
2
3
4
5
7
8
REFERENCES
1. Volovitz et al. Rapid induction of clinical response with a short-term high-dose starting schedule of budesonide
nebulizing suspension in young children with recurrent wheezing episodes. J Allergy Clin Immunol 1998;101:464-9.
2. Everard et al. Drug delivery developments. Respiratory Disease in Practice 2001; 18(2): 18-20
3. Smaldone GC et al. In vitro determination of inhaled mass and particle size distribution for budesonide nebulizing
suspension. J Aerosol Med 1998;11:113-125.