Colistin Powders with High Aerosolisation Efficiency for Respiratory Infection: Preparation and In Vitro Evaluation

Zhou, Qi Tony; Morton, David Alexander Vodden; Yu, Heidi H.; Jacob, Jovan; Wang, Jiping; Li, Jian; Chan, Hak‐Kim

doi:10.1002/jps.23685

Cited by 51 publications

(58 citation statements)

References 44 publications

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“…29 Primary particle sizes of colistin particles were in the range of 1−2 μm, which was in agreement with the laser diffraction results. In contrast, the rifapentine particles were elongated or rod-shaped.…”

Section: ■ Introductionsupporting

confidence: 83%

Novel Inhaled Combination Powder Containing Amorphous Colistin and Crystalline Rifapentine with Enhanced Antimicrobial Activities against Planktonic Cells and Biofilm of Pseudomonas aeruginosa for Respiratory Infections

et al. 2014

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Colistin has been increasingly used for the treatment of respiratory infections caused by Gram-negative bacteria. Unfortunately parenteral administration of colistin can cause severe adverse effects. This study aimed to develop an inhaled combination dry powder formulation of colistin and rifapentine for the treatment of respiratory infections. The combination formulation was produced by spray-drying rifapentine particles suspended in an aqueous colistin solution. The combination dry powder had enhanced antimicrobial activities against planktonic cells and biofilm cultures of Pseudomonas aeruginosa, with both minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) values (2 and 4 mg/L, respectively) being half that of pure colistin (MIC 4 mg/L and MBIC 8 mg/L) and 1/16th that of pure rifapentine (MIC 32 mg/L and MBIC 64 mg/L). High aerosol performance, as measured via an Aerolizer device, was observed with emitted doses>89% and fine particle fraction (FPF) total>76%. The proportion of submicron particles of rifapentine particles was minimized by the attachment of colistin, which increased the overall particle mass and aerodynamic size distribution. Using the spray-drying method described here, stable particles of amorphous colistin and crystalline rifapentine were distributed homogeneously in each stage of the impinger. Unlike the colistin alone formulation, no deterioration in aerosol performance was found for the combination powder when exposed to a high relative humidity of 75%. In our previous study, surface coating by rifampicin contributed to the moisture protection of colistin. Here, a novel approach with a new mechanism was proposed whereby moisture protection was attributed to the carrier effect of elongated crystalline rifapentine particles, which minimized contact between hygroscopic colistin particles. This inhaled combination antibiotic formulation with enhanced aerosol dispersion efficiency and in vitro efficacy could become a superior treatment for respiratory infections.

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Section: ■ Introductionsupporting

confidence: 83%

Novel Inhaled Combination Powder Containing Amorphous Colistin and Crystalline Rifapentine with Enhanced Antimicrobial Activities against Planktonic Cells and Biofilm of Pseudomonas aeruginosa for Respiratory Infections

et al. 2014

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“…The environmental RH was increased from 0 to 90 % for the sorption cycle and then decreased from 90 to 0 % for desorption cycle at 10 % RH increments. Equilibrium moisture content at each testing RH was determined by a dm/dt of 0.002 % per minute (20). …”

Section: Methodsmentioning

confidence: 99%

“…The aerosolisation performance of such hygroscopic particles can be compromised under elevated humidities due to increased capillary forces between particles in contact. In our earlier study, inhalable powder formulations of colistin were developed by the spray drying approach without any additives (20). The spray-dried amorphous colistin powder absorbed up to 30 %w/w water when it was stored at high RH > 60 %.…”

Section: Introductionmentioning

confidence: 99%

How Much Surface Coating of Hydrophobic Azithromycin Is Sufficient to Prevent Moisture-Induced Decrease in Aerosolisation of Hygroscopic Amorphous Colistin Powder?

Zhou

Loh²,

et al. 2016

AAPS J

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Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprise two drugs in the designed mass ratio, which is supported by XPS and ToF-SIMS data. XPS and ToF-SIMS measurements also revealed that 50 % by weight (or 35 % by molecular fraction) of azithromycin in the formulation provided a near-complete coating of 96.5 % (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in FPFrecovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20 %w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture.

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“…A few studies reported that excipient-free antibiotic (e.g. colistin) spray-dried powders have miraculous aerosolization performance [9], and the combination of different antibiotics (e.g. colistin and rifampicin) can create spray-dried powders with multifunctional characteristics of high delivery efficiency and moisture protection [10].…”

Section: Introductionmentioning

confidence: 99%

The influence of amino acids on aztreonam spray-dried powders for inhalation

Yang

Qu³

et al. 2015

Asian Journal of Pharmaceutical Sciences

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Available online A B S T R A C TThe dry powder inhalation of antibiotics for the treatment of lung infections has attracted drastically increasing attention as it offers rapid local therapy at lower doses and minimal side effects. In this study, aztreonam (AZT) was used as the model antibiotic and spraydried to prepare powders for inhalation. Amino acids of glycine (GLY), histidine (HIS) and leucine (LEU) were used as excipients to modify the spray-dried particles. It was demonstrated that the GLY-AZT spray-dried powders formed huge agglomerates with the size of 144.51 μm, which made it very difficult to be delivered to the lungs (FPF: 0.29% w/w only).In comparison with the AZT spray-dried powders, HIS-modified spray-dried powders showed increased compressibility, indicating larger distance and less cohesion between particles; while the LEU-modified spray-dried particles showed a hollow structure with significantly decreased densities. The fine particle fraction for HIS-and LEU-modified powders was 51.4% w/w and 61.7% w/w, respectively, and both were significantly increased (one-way ANOVA, Duncan's test, P < 0.05) compared to that of AZT spray-dried powders (45.4% w/w), showing a great potential to be applied in clinic. © 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Shenyang Pharmaceutical University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Colistin Powders with High Aerosolisation Efficiency for Respiratory Infection: Preparation and In Vitro Evaluation

Cited by 51 publications

References 44 publications

Novel Inhaled Combination Powder Containing Amorphous Colistin and Crystalline Rifapentine with Enhanced Antimicrobial Activities against Planktonic Cells and Biofilm of Pseudomonas aeruginosa for Respiratory Infections

Novel Inhaled Combination Powder Containing Amorphous Colistin and Crystalline Rifapentine with Enhanced Antimicrobial Activities against Planktonic Cells and Biofilm of Pseudomonas aeruginosa for Respiratory Infections

How Much Surface Coating of Hydrophobic Azithromycin Is Sufficient to Prevent Moisture-Induced Decrease in Aerosolisation of Hygroscopic Amorphous Colistin Powder?

The influence of amino acids on aztreonam spray-dried powders for inhalation

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