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Effects of Surface Composition on the Aerosolisation and Dissolution of Inhaled Antibiotic Combination Powders Consisting of Colistin and Rifampicin
- Source :
- The AAPS Journal. 18:372-384
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Colistin is often the only effective antibiotic against the respiratory infections caused by multidrug-resistant Gram-negative bacteria. However, colistin-resistant multidrug-resistant isolates have been increasingly reported and combination therapy is preferred to combat resistance. In this study, five combination formulations containing colistin (COL) and rifampicin (RIF) were prepared by spray drying. The lowest minimum inhibitory concentration (MIC) value against Pseudomonas aeruginosa PAO1 was measured for the formulation of COL/RIF = 4:1 with relatively high emitted doses (over 80%) and satisfactory fine particle fractions (over 60%). Data from X-ray photoelectron spectroscopy (XPS) and nano-time-of-flight secondary ion mass spectrometry (ToF-SIMS) showed the surfaces of particles were mainly covered by rifampicin even for the formulation with a mass ratio of COL/RIF = 4:1. Because colistin is hygroscopic and rifampicin is hydrophobic, moisture absorption of combination formulations was significantly lower than the pure colistin formulation in the dynamic vapour sorption results. To investigate the dissolution characteristics, four dissolution test methods (diffusion Franz cell, modified Franz cell, flow-through and beaker methods) were employed and compared. The modified Franz cell method was selected to test the dissolution behaviour of aerosolised powder formulations to eliminate the effect of membrane on dissolution. The results showed that surface enrichment of hydrophobic rifampicin neither affected aerosolisation nor retarded dissolution rate of colistin in the combination formulations. For the first time, advanced surface characterisation techniques of XPS and ToF-SIMS have shown their capability to understand the effect of surface composition on the aerosolisation and dissolution of combination powders. Refereed/Peer-reviewed
- Subjects :
- Surface Properties
Stereochemistry
Pharmaceutical Science
Microbial Sensitivity Tests
02 engineering and technology
rifampicin
030226 pharmacology & pharmacy
03 medical and health sciences
Minimum inhibitory concentration
dry powder inhaler
0302 clinical medicine
respiratory infection
Administration, Inhalation
polycyclic compounds
medicine
Dissolution testing
colistin
combination antibiotics
Particle Size
Solubility
Respiratory Tract Infections
Dissolution
Aerosols
Colistin
Chemistry
Respiratory infection
Dry Powder Inhalers
biochemical phenomena, metabolism, and nutrition
bacterial infections and mycoses
021001 nanoscience & nanotechnology
Anti-Bacterial Agents
Spray drying
Pseudomonas aeruginosa
Particle size
Rifampin
0210 nano-technology
Research Article
Nuclear chemistry
medicine.drug
Subjects
Details
- ISSN :
- 15507416
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- The AAPS Journal
- Accession number :
- edsair.doi.dedup.....33f49ca4759188f223a508ac15124cc3