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. 2014 Oct;6(10):1411-9.
doi: 10.3978/j.issn.2072-1439.2014.08.38.

Experimentation with aerosol bonsetan, pirfenidone, treprostinil and sidenafil

Haidong Huang  1 , Paul Zarogoulidis  1 , Sofia Lampaki  1 , John Organtzis  1 , Dimitris Petridis  1 , Konstantinos Porpodis  1 , Antonis Papaiwannou  1 , Vasilis Karageorgiou  1 , Georgia Pitsiou  1 , Ioannis Kioumis  1 , Wolfgang Hohenforst-Schmidt  1 , Qiang Li  1 , Kaid Darwiche  1 , Lutz Freitag  1 , Aggeliki Rapti  1 , Konstantinos Zarogoulidis  1
Affiliations

Experimentation with aerosol bonsetan, pirfenidone, treprostinil and sidenafil

Haidong Huang et al. J Thorac Dis. 2014 Oct.

Abstract

Introduction: Pulmonary hypertension (PH) has been identified either as a symptom or a primary entity. Several drugs are already on the market and other are being investigated. Idiopathic pulmonary fibrosis (IPF) is also a disease were several drugs are being investigated.

Materials and methods: Three jet nebulizers and three ultrasound nebulizers were used for our experiments with seven different residual cups and four different loadings. Bonsetan, treprostinil, sidenafil and pirfenidone were modified in order to be produced as aerosol in an effort to identify parameters which influence the droplet size production size.

Results: The four-way ANOVA on droplet size using the jet nebulizers revealed two statistically significant factors, drug (F=6.326, P=0.0007) and residual cup (F=4.419, P=0.0007), and their interaction term (F=5.829, P<0.0001). Drugs bonsetan and pirfenidone produce equally the lowest mean droplet size (2.63 and 2.80 respectively) as compared to other two drug mean sizes. The ANOVA results, concerning the ultrasound nebulizers, revealed only the nebulizers as producing significant effect on droplet size (F=4.753, P=0.037).

Discussion: Our study indicates the importance of the initial drug design formulation. Moreover, further investigation of the residual cup design is an additional parameter that can assist in the optimal droplet size production, indifferently of the drug formulation.

Keywords: Pulmonary hypertension (PH); aerosol; bonsetan; interstitial lung fibrosis; pirfenidone.

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Figures

Figure 1
Figure 1
Jet-nebulizer.
Figure 2
Figure 2
Large residual cups 10 mLs max.
Figure 3
Figure 3
Small residual cups 6 mLs max.
Figure 4
Figure 4
Ultrasound nebulisers.
Figure 5
Figure 5
Matersizer 2000.
Figure 6
Figure 6
Milling equipment.
Figure 7
Figure 7
Kern digital scale.
Figure 8
Figure 8
Mean droplet size distribution of four drugs. Vertical bars represent the 95% confidence intervals of the means calculated from the error mean square of ANOVA.
Figure 9
Figure 9
Mean droplet size distribution of seven residual cups. Vertical bars represent the 95% confidence intervals of the means calculated from the error mean square of ANOVA.
Figure 10
Figure 10
Mean droplet size distribution of the combined levels between drugs and residual cups. Vertical bars represent the 95% confidence intervals of the means calculated from the error mean square of ANOVA.
Figure 11
Figure 11
Mean droplet size distribution of three ultrasound nebulizers. Vertical bars represent the 95% confidence intervals of the means calculated from the error mean square of ANOVA.
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