THE STABILITY OF THE INHALED CORTICOSTEROIDS BUDESONIDE AND FLUTICASONE PROPIONATE DURING NEBULISATION

A.Szczawinska-Poplonyk. J.Alkiewicz

Department of Paediatric Pneumonology, University of Medical Sciences, Poznan,Poland

OBJECTIVE: Inhaled conicosteroid therapy is currently the principle of the long-term anti-inflammatory treatment of bronchial asthma in children. Clinical efficacy and safety for a patient of such therapy is an indispensable condition, to the process of aerosol generation the influence of nebulisation on the stability of the corticosteroids applied via inhalation route may lead to the change of their pharmacokinetic and pharmacodynamic features. The purpose of the study was to assess the stability of the inhaled corticosteroids budesonide and fluticasone propionate during nebulisation with employment of ultrasonic and jet procedures.

METHODS: Two preparations of corticosteroids ready for nebulisation were used in this research: 0,0125% water suspension of budesonide and 0,0125% water suspension of fluticasone propionate. Each of these preparations was converted into aerosol by means of the following techniques: ultrasonic method - in De Vilbiss inhalation device and jet method - in Sidestream inhalation vessel (the latter method using either compressed atmospheric air or pure oxygen as aerosol carriers). Standard solution samples, obtained liquefied aerosol samples and remnants of the nebulised solution from inhalation devices were analyzed using HPLC. The obtained chromatograms were compared with the chromatograms of the standard solutions of the same steroids.

RESULTS: On the basis of qualitative analysis of costicosteroids in the collected samples carried out by HPLC, destabilisation of budesonide nebulised by ultrasounds was shown. It manifested as an additional peak on chromatograms corresponding with a break-down product appearence. The relative amount of the newly originated compound of budesonide aerosol was estimated to 7,3%. The same was not proven with respect to budesonide nebulised by means of air-and oxygen -jet methods. No destabilisation was shown for fluticasone propionate for any of the aerosol generation methods applied.

CONCLUSIONS: Currently employed methods of aerosol generation may lead to destabilisation of corticosteroids applied via inhalation route, hovewer the susceptibility of corticosteroids to different factors is heterogenous. Thus the methods of corticosteroids nebulisation considered to be safe are: 1. with respect to budesonide - air - and oxygene -jet methods, whereas 2. with respect to fluticasone propionate - both ultrasonic and jet ones. Our results imply the necessity to individually select the corticosteroid preparation as well as the method of nebulisation which allows to avoid destabilisation of the inhaled drug and to provide for maximal safety of the inhalation therapy.