Physicochemical compatibility of nebulizable drug admixtures containing budesonide and colistimethate or hypertonic saline.

Knowledge of the physicochemical compatibility of admixtures of nebulizable drugs is an important issue. In this article, the results of our recent study dealing with the compatibility of drug admixtures containing budesonide and colistin methanesulfonate (brand name Colistin CF) or budesonide and 5.85% sodium chloride solution are presented, as well as the up-to-date version of our compatibility table. Admixtures were prepared by mixing 2.0 mL Pulmicort either with 3.0 mL Colistin CF or 4.0 mL 5.85% sodium chloride solution. Test solutions were stored for 24 hours at room temperature under ambient light conditions. Physical compatibility was determined by measuring pH and osmolality. Concentrations of budesonide were measured by a high-performance liquid chromatography assay. The antibiotic activity of colistin methanesulfonate was determined in comparison to standard solutions using a microbiological assay. No loss in drug concentration of budesonide and no change in antibiotic activity of colistin methanesulfonate were detected over a test period of 24 hours. Osmolality remained unchanged in both types of admixtures. In admixtures of budesonide with colistin methanesulfonate, pH increased during the first 4 hours of storage, while in admixtures of budesonide and hypertonic saline pH remained unchanged. No visible changes could be detected. Due to these results admixtures of budesonide and colistin methanesulfonate or 5.85% sodium chloride solution are designated to be compatible, but it is recommended that mixing should take place immediately before administration. Further investigations are needed to determine whether or not drug delivery is affected by mixing the drugs and to ensure simultaneous nebulization is recommendable.