Compatibility of arformoterol tartrate inhalation solution with three nebulized drugs

ABSTRACT

Objective: Arformoterol tartrate inhalation solution (15 μg/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 μg/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 (T₀) and 30 min (T₃₀) 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 T₀ 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 T₀ and T₃₀, 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 T₃₀ 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.

Key words: :

• Admixing
• Arformoterol
• Compatibility
• HPLC analysis
• Inhalation solution
• Mixing