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.
Zusammenfassung
Ziel Der Erfolg einer Inhalationstherapie wird durch Menge und Qualität des inhalierten Aerosols bestimmt. Die Auswahl eines Verneblers bedarf der Kenntnis der entsprechenden Aerosolcharakteristika.
Methoden Die Aerosolperformance von 9 marktüblichen Druckluftverneblern wurde in vitro in 2 Simulationsmodellen geprüft. Salbutamol (Sultanol forte® Fertiginhalat 2,5 mg/2,5 ml; GSK) wurde über 4 Minuten vernebelt. Die Outputparameter wurden mit dem Atemzugsimulator PARI Compas II (Erwachsenenmanöver nach Ph.Eur.9.0; n = 5/6 Verneblungen) und die aerodynamische Partikelgrößenverteilung mit dem Next Generation Impaktor (Ph.Eur.9.0, Copley Scientific; n = 3 Verneblungen) per HPLC bestimmt.
Ergebnisse Die Vernebler generierten deutlich unterschiedliche Abgaberaten und Aerosolspektren. Die Drug Delivery Rate (DDR) variierte zwischen 196 µg/min (PARI LC Sprint (blau)) und 67 µg/min (MIDINEB). Die aus DDR und Feinpartikelanteil ≤ 5 µm berechnete intrapulmonal deponierte Aerosolmenge (Respirable Drug Delivery Rate, RDDR) variierte um den Faktor 3,5.
Schlussfolgerungen Die Ergebnisse der In-vitro-Untersuchungen können unterstützend zur Auswahl eines geeigneten Druckluftverneblers genutzt werden. Für eine effektive Therapie und gute Compliance sollte ein Vernebler mit einer hohen RDDR gewählt werden.
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