Stability of commonly nebulized drugs in heated and humid condition

Abstract

Placement of nebulizer prior to heated humidifier has been reported to improve efficiency of aerosol delivery during ventilator support. Drugs nebulized in this position must travel through humidifier, rainout in reservoir and may be subjected to extended periods of heat up to 50°C. Toxic degradation may develop, posing potential risk to patient. The aim of this study was to evaluate chemical stability of commonly inhaled drugs administered to mechanically ventilated patients subjected to extended period of 50°C. Formulations of 8 comonly inhaled drugs were diluted to 50 mL total volume in water and exposed to 50oC for 7 days to simulate effect of heat in humidifier. High Performance Liquid Chromatography (HPLC) was performed before and after heating to determine drug stability and degradation. Drug integrity, color or pH changes were noted. Epinephrine, levalbuterol, tobramycin and colistin demonstrated>10% reduction in concentration but only acetylcysteine had additional peaks in HPLC chromatogram demonstrating potential degradation and possible production of by product. Changes in color were observed with epinephrine and acetylcysteine. All drugs retained their integrity after subjecting them to 50oC for 7 days except acetylcysteine. Acetylcysteine changed color and had new peak in HPLC chromatogram. Color change with epinephrine was not associated with any new peak in HPLC chromatogram. Further studies should determine whether acetylcysteine changes would result in any off gassing of vapor that might harm the patient.