Jane E McKenzie1, Mario Cruz-Rivera. 1. Analytical Development, QAAS Method Services, AstraZeneca LP, 50 Otis Street, Westborough, MA 01581-4500, USA. jane1.mckenzie@astrazeneca.com
Abstract
BACKGROUND: Nebulizable medications often are mixed to simplify asthma medication regimens. OBJECTIVE: To establish the in vitro chemical compatibility and stability of budesonide inhalation suspension 0.25 mg/2 mL and 0.5 mg/2 mL mixed in Pari LC Plus jet nebulizer cups with 3 mL of levalbuterol hydrochloride 0.63 mg/3 mL and 1.25 mg/3 mL; 0.5 mL of albuterol sulfate 5 mg/mL; 2 mL of cromolyn sodium 20 mg/2 mL; or 2.5 mL of ipratropium bromide 0.2 mg/mL. METHODS: We developed and validated isocratic HPLC methods to permit separation of the admixture components from aliquots taken 0, 5, 15, and 30 minutes after mixing. Admixtures were prepared and analyzed at room temperature. Each assay was conducted 3 times using separate nebulizer cups. All components were quantified by external standards using HPLC-derived peak area. Appearance and pH of the admixtures were recorded. RESULTS: No additional peaks occurred in any HPLC chromatogram for any medication from any admixture. With the exception of ipratropium bromide at 93%, each admixture retained >97% of the initial concentration of each medication in the nebulizer cup. There was no significant change in pH or visual identification of a precipitate in any admixture of active drugs. CONCLUSIONS: These data support the chemical compatibility of budesonide inhalation suspension for up to 30 minutes with other commonly used nebulized medications for controlling pediatric asthma symptoms.
BACKGROUND: Nebulizable medications often are mixed to simplify asthma medication regimens. OBJECTIVE: To establish the in vitro chemical compatibility and stability of budesonide inhalation suspension 0.25 mg/2 mL and 0.5 mg/2 mL mixed in Pari LC Plus jet nebulizer cups with 3 mL of levalbuterol hydrochloride 0.63 mg/3 mL and 1.25 mg/3 mL; 0.5 mL of albuterol sulfate 5 mg/mL; 2 mL of cromolyn sodium 20 mg/2 mL; or 2.5 mL of ipratropium bromide 0.2 mg/mL. METHODS: We developed and validated isocratic HPLC methods to permit separation of the admixture components from aliquots taken 0, 5, 15, and 30 minutes after mixing. Admixtures were prepared and analyzed at room temperature. Each assay was conducted 3 times using separate nebulizer cups. All components were quantified by external standards using HPLC-derived peak area. Appearance and pH of the admixtures were recorded. RESULTS: No additional peaks occurred in any HPLC chromatogram for any medication from any admixture. With the exception of ipratropium bromide at 93%, each admixture retained >97% of the initial concentration of each medication in the nebulizer cup. There was no significant change in pH or visual identification of a precipitate in any admixture of active drugs. CONCLUSIONS: These data support the chemical compatibility of budesonide inhalation suspension for up to 30 minutes with other commonly used nebulized medications for controlling pediatric asthma symptoms.