Physicochemical compatibility of fluticasone-17-propionate nebulizer suspension with ipratropium and albuterol nebulizer solutions

Wolfgang Kamin¹, Astrid Schwabe², Irene Krämer²

¹Childrens Hospital, Johannes Gutenberg-Universität, Langenbeckstraße 1, D-55101 Mainz, Germany; ²Department of Pharmacy, Johannes Gutenberg-Universität, Langenbeckstraße 1, D-55101 Mainz, Germany

Abstract: The objective of this in-vitro study was to determine whether mixtures of three nebulizable drugs are physicochemically compatible. Drug combinations were prepared by mixing the content of one respule Flutide^® forte “ready to use” (fluticasone propionate) with 2 milliliter Atrovent^® LS (ipratropium bromide) and 0.5 milliliter Sultanol^® inhalation solution (albuterol sulfate). Test suspensions were stored at room temperature and exposed to normal laboratory light for 5 hours. Concentrations of fluticasone-17-propionate, ipratropium bromide, and albuterol sulfate were determined by using stability-indicating high-performance liquid chromatography assays with ultraviolet detection. Physical compatibility was determined by measuring pH and osmolality. Main outcome measures were the drug concentrations of the active components of the mixtures. All drug concentrations retained nearly 100% of the initial drug concentrations after mixing and storage in glass containers at room temperature. Osmolality and pH of the mixtures exhibited no significant changes and no visible changes of the mixtures were detectable over the inspection period. Mixtures of fluticasone propionate, ipratropium bromide, and albuterol sulfate inhalation drug products were shown to be physicochemically compatible over a period of 5 hrs. In order to avoid contamination and microbiological instability, mixing should only take place immediately before administration. Further investigations are needed to determine whether or not drug delivery is affected by mixing the nebulizer suspensions and to ensure that simultaneous nebulization is recommendable.

Keywords: albuterol, compatibility, COPD, fluticasone, HPLC, inhalation, ipratropium, nebulizer