Physicochemical compatibility of nebuliser solution admixtures containing colistimethate and hypertonic saline or colistimethate, fluticasone-17-propionate, ipratropium bromide and salbutamol sulfate
- 1Department of Pharmacy, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany
- 2Pediatric Department, Lutherian Hospital Hamm, Hamm, Germany
- Correspondence to Dr Irene Krämer, Department of Pharmacy, University Medical Center, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, Mainz 55131, Germany;
Contributors HW-J and CS performed the experiments. HW-J and IK wrote the paper. WK reviewed the paper.
- Received 18 May 2012
- Revised 24 July 2012
- Accepted 30 July 2012
- Published Online First 30 August 2012
Objectives For practical reasons, patients with cystic fibrosis (CF) tend to mix different inhalation solutions for concomitant inhalation instead of inhaling the different medications consecutively. A study was undertaken to examine the compatibility of colistimethate dissolved in 5.85% hypertonic sodium chloride (NaCl) solution and the quadripartite mixtures of colistimethate, fluticasone-17-propionate, ipratropium bromide and salbutamol sulfate.
Methods The test solutions were prepared by mixing ordinary doses of the inhalation products and analysed immediately. Microbiological assays of antibiotics and high-performance liquid chromatography assays were used to determine chemical compatibility and visual inspection, pH and osmolality measurements were used to determine physical compatibility. Mixtures of colistimethate with NaCl solutions were stored in a refrigerator at 2–8°C for 48 h and retested.
Results The antimicrobial activity of colistimethate dissolved in 5.85% NaCl solution did not differ from the activity of colistimethate dissolved in 0.9% NaCl solution and remained unchanged over a period of 48 h. In the quadripartite admixtures the activity of colistimethate and the concentrations of ipratropium bromide, salbutamol sulfate and fluticasone-17-propionate amounted to ≥ 100% of the nominal concentrations. Chemical and physical compatibility was shown.
Conclusions When colistimethate is dissolved in 5.85% NaCl solution for inhalation, the antimicrobial activity remains unchanged over a period of 48 h. With regard to in vitro compatibility, simultaneous inhalation of quadripartite mixtures of colistimethate, fluticasone-17-propionate, salbutamol sulfate and ipratropium bromide or colistimethate in 5.85% NaCl solution is feasible but needs to be clinically confirmed.