Experimentation with aerosol bonsetan, pirfenidone, treprostinil and sidenafil

Haidong Huang, Paul Zarogoulidis, Sofia Lampaki, John Organtzis, Dimitris Petridis, Konstantinos Porpodis, Antonis Papaiwannou, Vasilis Karageorgiou, Georgia Pitsiou, Ioannis Kioumis, Wolfgang Hohenforst-Schmidt, Qiang Li, Kaid Darwiche, Lutz Freitag, Aggeliki Rapti, Konstantinos Zarogoulidis
Journal of Thoracic Disease 2014, 6 (10): 1411-9

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.

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