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									     Budesonide inhalation suspension delivered
    via Ventstream® breath-enhanced jet nebulizer

                          K. Nikander1, M. Cruz-Rivera2, and G.C. Smaldone3                                                                                                               Nikander01.indd/teb/IPC ISAM 2003
                                Profile Therapeutics plc, Bognor Regis, UK; 2AstraZeneca LP, Wilmington, DE;
                                           Pulmonary/Critical Care Medicine, SUNY, Stony Brook, NY

INTRODUCTION                                                                                  DISCUSSION
Ventstream (Profile Therapeutics) is a breath-enhanced jet nebulizer                          In Fig. 2 (modified from ref. 3) the inhaled mass of budesonide for the two
which has been shown clinically to be suitable for delivery of nebulized                      Ventstream nebulizers (bars 8 and 11) has been added to the inhaled mass
budesonide.1-2 In vitro studies have shown that the drug mass output, the
                                                                                              of budesonide of 27 other nebulizers. The inhaled mass of budesonide
droplet size and nebulization time will vary with the nebulizer and compres-
sor system used.3 The amount of drug inhaled (inhaled mass) will also                         achieved with the Ventstream nebulizer was comparable to that of the most
depend on the patient’s breathing pattern. It is therefore important to char-                 efficient previously tested nebulizers. The amount of budesonide in the respi-
acterize the jet nebulizer with the drug to be used in terms of inhaled mass                  rable fractions was, however, clearly larger than the other nebulizers.
and droplet size using a test setup that mimics the treatment situation.
                                                                                              Fig 2.

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.

                                                                                                     Nebulizer                     Compressor                          Nebulizer                     Compressor
                                                                                              1      Pari LC Jet Plus              Pulmo-Aide                   9      Hudson AVA-NEB                Pulmo-Aide

METHODS                                                                                       2
                                                                                                     Pari LC Jet Plus
                                                                                                     Baxter Misty Neb
                                                                                                     Hudson T Updraft II
                                                                                                                                   Pari Master
                                                                                                                                                                       Pari LC Jet
                                                                                                                                                                       Hudson AVA-NEB
                                                                                                                                                                                                     CR 60
                                                                                                                                                                                                     Pari Master
The Ventstream nebulizer was connected via a filter to a Harvard                              7      Hudson T Updraft II           Hudson                       15     Pari LC Jet                   Pulmo-Aide
                                                                                              8      Ventstream                    Passport                     16     DeVilbiss Pulmo-Neb           Pulmo-AideTraveller
sinus pump which generated a simulated breathing pattern (VT 200ml,                                                                                             22     DeVilbiss Pulmo-Neb           Pulmo-Aide

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 compres-
sor. 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.
                                                                                                     For budesonide inhalation suspension delivery,
Fig. 1a.
                                                                                                     the inhaled mass of the Ventstream jet nebulizer
                                                                                                     is comparable to that of other efficient jet
                                                                                                     The respirable fraction of the inhaled mass
                                                                                                     of budesonide achieved with Ventstream is,
Fig 1.b                                                                                              however, larger.
                                                                                                     The positive ratio of respirable fraction :
                                                                                                     inhaled mass achieved with the Ventstream
                                                                                                     nebulizer should in clinical practice minimize
                                                                                                     oropharyngeal deposition and increase lung
RESULTS                                                                                       REFERENCES
The nebulization times to dryness were 7.3 min for Ventstream/Passport and                    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.
9.1 min for Ventstream/Pulmo-Aide. The mean inhaled and exhaled masses                        2. Everard et al. Drug delivery developments. Respiratory Disease in Practice 2001; 18(2): 18-20
of budesonide, the MMAD and the amount of budesonide in the respirable                        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.
fractions are shown in the table below.
                                                                    Respirable   Respirable
                         Inhaled        Exhaled        MMAD
Nebulizer/compressor                                                 fraction     fraction
                        mass (sd)       mass (sd)      (GSD)
                                                                      ≤ 6 µm      ≤ 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 %

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