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Comparison between Colistin Sulfate Dry Powder and Solution for Pulmonary Delivery
Frédéric Tewes1,2, Julien Brillault1,2, Nicolas Gregoire1,2
1INSERM U1070 "Pharmacology of anti-infective agents", 1 rue Georges Bonnet, Pôle Biologie Santé, 86022 Poitiers Cedex, France.
Pharmaceutics
|June 21, 2020
Summary
Pulmonary delivery of colistin (COLI) powder resulted in higher lung concentrations compared to solution, suggesting faster absorption. This difference is linked to increased colistin permeability at high local concentrations in the lung.
Area of Science:
- Pharmacology
- Drug Delivery
- Respiratory Medicine
Background:
- Pulmonary delivery of antibiotics like colistin (COLI) is crucial for treating lung infections.
- Understanding the pharmacokinetic differences between inhaled COLI powder and solution is essential for optimizing therapy.
- Colistin's efficacy is often limited by its pharmacokinetic profile in the lungs.
Purpose of the Study:
- To compare the pulmonary fate of colistin when delivered as a powder versus a solution.
- To evaluate the pharmacokinetic properties of inhaled colistin formulations in a rat model.
- To investigate the impact of local drug concentration on colistin's apparent permeability.
Main Methods:
- Development and characterization of amorphous colistin powder using spray drying.
- Pulmonary administration of colistin powder (via Handihaler®) and solution in rats.
- Measurement of colistin concentrations in pulmonary epithelial lining fluid (ELF) and plasma over time.
- Assessment of colistin apparent permeability (Papp) across a Calu-3 cell model at varying concentrations.
Main Results:
- Colistin powder exhibited favorable aerodynamic properties (MMAD 2.68 µm, FPF 59.5%).
- Pulmonary ELF:plasma AUC ratios were significantly higher for the colistin solution (570) than the powder (95).
- Despite differing ELF concentrations, plasma concentration profiles were similar, suggesting faster systemic absorption from the powder.
- Colistin Papp across Calu-3 cells increased 10-fold with concentration, indicating concentration-dependent permeability.
Conclusions:
- Inhaled colistin powder leads to higher local lung concentrations compared to solution, potentially due to faster systemic absorption.
- The observed in vivo differences may be driven by a concentration-dependent increase in colistin's apparent permeability at the site of powder impaction in the lung.
- High local colistin concentrations can enhance epithelial transfer and overall absorption rate, offering a potential strategy for improved pulmonary antibiotic delivery.
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