Effects of Surface Composition on the Aerosolisation and Dissolution of Inhaled Antibiotic Combination Powders Consisting of Colistin and Rifampicin
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Effects of Surface Composition on the Aerosolisation and Dissolution of Inhaled Antibiotic Combination Powders Consisting of Colistin and Rifampicin. / Wang, Wenbo; Zhou, Qi Tony; Sun, Si-Ping; Denman, John A; Gengenbach, Thomas R; Barraud, Nicolas; Rice, Scott A; Li, Jian; Yang, Mingshi; Chan, Hak-Kim.
In: A A P S Journal, Vol. 18, No. 2, 03.2016, p. 372-84.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effects of Surface Composition on the Aerosolisation and Dissolution of Inhaled Antibiotic Combination Powders Consisting of Colistin and Rifampicin
AU - Wang, Wenbo
AU - Zhou, Qi Tony
AU - Sun, Si-Ping
AU - Denman, John A
AU - Gengenbach, Thomas R
AU - Barraud, Nicolas
AU - Rice, Scott A
AU - Li, Jian
AU - Yang, Mingshi
AU - Chan, Hak-Kim
PY - 2016/3
Y1 - 2016/3
N2 - 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.
AB - 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.
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1208/s12248-015-9848-z
DO - 10.1208/s12248-015-9848-z
M3 - Journal article
C2 - 26603890
VL - 18
SP - 372
EP - 384
JO - A A P S Journal
JF - A A P S Journal
SN - 1550-7416
IS - 2
ER -
ID: 169133952