The Science Journal of the American Association for Respiratory Care

2008 OPEN FORUM Abstracts

PHYSICOCHEMICAL COMPATIBILITY AND IN VITRO DEPOSITION PROPERTIES OF FORMOTEROL FUMARATE INHALATION SOLUTION BINARY ADMIXTURES WITH FOUR NEBULIZABLE MEDICATIONS

Samuel Akapo1, June Gupta1, Eloisa Martinez1, Chithra McCrea1, Liwen Ye1, Mark Roach1



Background: Drug delivery by nebulization is often administered by co-mixing the medications for patients that require multiple doses of different nebulizable drugs per day to simplify treatment. However, admixing may alter the physicochemical and aerodynamic properties of the medications due to possible interactions between the drugs and/or their formulation components. This study examined the physicochemical compatibility and aerodynamic characteristics of a newly approved long-acting b-agonist (LABA) nebulized drug for COPD patients, formoterol fumarate, 20mcg/2mL, when mixed or sequentially administered with budesonide suspension 0.5mg/2mL; ipratropium bromide 0.5mg/2.5mL; cromolyn sodium 20mg/2mL; or acetylcysteine 10% (100mg/mL).

Methods: The admixtures were prepared in triplicate and analyzed for physicochemical compatibility from 0-60 minutes after mixing. Physical compatibility was determined by visual examination and pH, osmolality and turbidity measurements. Chemical stability was evaluated using stability-indicating high-performance liquid chromatography assay methods. The aerodynamic characteristics of the admixtures were determined from aerosols generated from Pari LC Plus nebulizer using an 8-stage cascade impactor.

Results: The admixtures remained as clear, colorless solutions with no precipitation except for the cloudiness observed in formoterol/budesonide combination due to budesonide suspension. The pH, osmolality, and turbidity for all admixtures were within the initial values (≤3%), and there were no significant changes (≤2%) in potency of the active components throughout the 1-hour study period. Presumably due to increase drug volume or re-concentration in the nebulizer cup, the respirable fraction and the emitted dose for all drugs significantly (p<0.05) increased when nebulized as an admixture or sequentially (see Figure). However, the fine particle fraction (FPF), mass median aerodynamic diameter and geometric standard deviation generally remained unchanged for all admixtures with the exception of FPF for formoterol/budesonide combinations.

Conclusion: Our results indicate admixtures of formoterol with budesonide, ipratropium, cromolyn or acetylcysteine are physically and chemically compatible. However, admixing or sequential nebulization significantly increased the amount of drug delivered compared with single drug nebulization. The implications of the in-vitro results in the clinical setting have not been determined.