ABSTRACT
BACKGROUND: Medications are frequently combined in the nebulizer cup, so it is important to determine their chemical and physical compatibility. OBJECTIVE: To determine the chemical and physical compatibility of levalbuterol with ipratropium bromide, cromolyn sodium, acetylcysteine sodium, and budesonide. METHODS: We mixed one dose of levalbuterol inhalation solution concentrate (1.25 mg/0.5 mL) with one dose of ipratropium bromide (0.5 mg/2.5 mL), cromolyn sodium (20 mg/2 mL), acetylcysteine sodium (1,000 mg/5 mL), or budesonide (0.5 mg/2 mL). Immediately after mixing the 2 drugs (time zero [T(0)]), and again after 30 min at room temperature (T(30)), we visually inspected the admixtures, measured their pH, and conducted high-pressure liquid chromatography (HPLC). RESULTS: There was no evidence of physical incompatibility with these drugs combinations. With all the admixtures, both drugs were chemically stable for at least 30-min. Admixture pH had not changed significantly at T(30). Drug recovery was 93.2-102.6% of the initial or control values. CONCLUSIONS: The 2-drug admixtures we studied were compatible for at least 30 min at room temperature.
Subject(s)
Acetylcysteine/chemistry , Albuterol/chemistry , Budesonide/chemistry , Cromolyn Sodium/chemistry , Ipratropium/chemistry , Respiratory System Agents/chemistry , Acetylcysteine/administration & dosage , Administration, Inhalation , Albuterol/administration & dosage , Budesonide/administration & dosage , Cromolyn Sodium/administration & dosage , Drug Incompatibility , Drug Stability , Drug Therapy, Combination , Ipratropium/administration & dosage , Respiratory System Agents/administration & dosage , Time FactorsABSTRACT
OBJECTIVE: Arformoterol tartrate inhalation solution (15 microg/2 mL) is approved for the twice-daily, long-term maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary diseases (COPD). This study assessed the chemical and physical compatibility of arformoterol (15 microg/2 mL) with ipratropium bromide (0.5 mg/2.5 mL), acetylcysteine (800 mg/4 mL), and budesonide (0.25 mg/2 mL and 0.5 mg/2 mL). METHODS: Immediately (T(0)) and 30 min (T(30)) after preparation, the admixtures were tested by visual inspection, pH measurement, and HPLC assay of each active component. RESULTS: For all admixtures, no visible signs of change were observed. The pH of all admixtures at T(0) ranged from 4.82 to 6.40, which was within the range of individual drugs. For all admixtures, no unacceptable changes (less than 1% or 0.1 pH unit) in the pH values were observed within 30 min compared with the initial pH values in the admixtures, which met acceptance criteria of not more than (NMT) 10.0%. At both T(0) and T(30), the assay of each active component in all admixtures ranged from 98.3% to 101.4% compared to the assay in control samples, which met acceptance criteria of NMT 10.0%. In addition, no changes (less than 8%) in the assay of each active component at T(30) were observed compared to the initial assay values, which met acceptance criteria of NMT 10.0%. This study did not evaluate the clinical efficacy or safety of mixing arformoterol in patients. Nor did the study assess the aerosol characteristics of these admixtures or any potential changes in drug output. CONCLUSION: The results demonstrated that arformoterol was chemically and physically compatible with commercially available nebulized formulations of ipratropium bromide, acetylcysteine, and budesonide.
