Cospray Dried Antibiotics for Dry Powder Lung Delivery

Adi, Handoko; Young, Paul M.; Chan, Hak‐Kim; Stewart, Peter; Agus, Helen; Traini, Daniela

doi:10.1002/jps.21239

Cited by 72 publications

(33 citation statements)

References 30 publications

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“…In preclinical studies, gentamicin doses of 160-180 mg (micronized into dry powder) (31,32) and tobramycin doses of 13 mg (as 25 mg of PulmoSphere® particles) (33) have been used in healthy volunteers and those affected with CF; 20 mg doses of particulate ciprofloxacin, doxycycline, or co-spray-dried ciprofloxacin-doxycycline were used in a recently-reported formulation study (34). Anti-P. aeruginosa MIC 90 of gentamicin is 5 μg/ml (35), that of ciprofloxacin is less than 0.5 μg/ml (36), and that of ceftazidime is 2 μg/ml (37).…”

Section: Discussionmentioning

confidence: 99%

Microparticles for Inhalational Delivery of Antipseudomonal Antibiotics

Tsifansky

Yeo

Evgenov

et al. 2008

AAPS J

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Abstract. Chronic pseudomonal bronchopulmonary infections in cystic fibrosis patients are frequently controlled with inhaled antibiotics. Dry-powder inhalable antibiotics are an attractive alternative to nebulized medications. We produced and evaluated microparticles composed of dipalmitoylphosphatidylcholine, albumin, and lactose as a model system for intrapulmonary delivery of ceftazidime, ciprofloxacin, and several combinations of the two, none of which is presently available for inhalation. Microparticles containing one or both antibiotics were prepared by spray-drying. Their Anderson cascade impactor deposition profiles showed 10-30% fine particle fractions of the nominal dose. Microparticles containing varying amounts of each antibiotic showed statistically different deposition profiles. Aerodynamics and deposition of microparticles co-encapsulating both antibiotics were similar to those of single-drug microparticles with the same proportion of ciprofloxacin alone. The antipseudomonal activities of microparticles co-encapsulating half of the 50% effective concentration (EC 50 ) of both ceftazidime and ciprofloxacin (5 mg of particles containing 5% ceftazidime and 10% ciprofloxacin) were at least additive compared to particles containing the EC 50 of each antibiotic separately (5 mg of particles containing 10% ceftazidime or 5 mg of particles containing 20% ciprofloxacin). Co-encapsulation of the antibiotics in microparticles ensures co-deposition at desired ratios, improves the particles' aerodynamics and fine particle fraction, as compared to microparticles with equivalent amounts of ceftazidime alone, and achieves additive antipseudomonal activity.

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Section: Discussionmentioning

confidence: 99%

Microparticles for Inhalational Delivery of Antipseudomonal Antibiotics

Tsifansky

Yeo

Evgenov

et al. 2008

AAPS J

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“…This may be attributed to glass transition followed by a peak of crystallisation. 25) This suggests the presence of solid dispersion of the amorphous drug in the polymer matrix.…”

Section: Dišerential Scanning Calorimetrymentioning

confidence: 98%

Formulation Optimization and Characterization of Spray Dried Microparticles for Inhalation Delivery of Doxycycline Hyclate

Mishra

2011

YAKUGAKU ZASSHI

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The local delivery of antibiotics in the treatment of infectious respiratory diseases is an attractive alternative to deliver high concentration of antimicrobials directly to the lungs and minimize systemic side eŠects. In this study, inhalable microparticles containing doxycycline hyclate, sodium carboxymethylcellulose, leucine and lactose were prepared by spray drying of aqueous ethanol formulations. Box-Behnken design was used to study the in‰uence of various independent variables such as polymer concentration, leucine concentration, ethanol concentration and inlet temperature of the spray dryer on microparticle characteristics. The microparticles were characterized in terms of particle morphology, drug excipient interaction, yield, entrapment e‹ciency, Carr's index, moisture content, thermal properties, X-ray powder diŠraction, aerosolization performance and in vitro drug release. The eŠect of independent variables on spray dryer outlet temperature was also studied. The overall shape of the particles was found to be spherical like doughnuts in the size range of 1.16 5.2 mm. The optimized formulation (sodium carboxymethylcellulose concentration 14％ w/v, leucine concentration 33％ w/v, ethanol concentration 36％ v/v, inlet temperature of 140°C) exhibited the following properties: yield 56.69％, moisture content 3.86％, encapsulation e‹ciency 61.74％, theoretical aerodynamic diameter 3.11 mm and Carr's index 23.5％ at an outlet temperature 77°C. The powders generated were of a suitable mass median aerodynamic diameter (4.89 mm) with 49.3％ˆne particle fraction and exhibited a sustained drug release proˆle in vitro.

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“…Adi et al [43] used spray-drying method to produce dry powders for inhalation-containing doxycycline or ciprofloxacin or even a combination of these two chemicals. The cospray formulation of doxycycline and ciprofloxacin (1:1 ratio) has proved to be more efficient for lung delivery than each one of the single spray-dried antibiotic since it exhibited improved physical stability which favored the drug deposition profile.…”

Section: Pulmonary Drug Deliverymentioning

confidence: 99%

Spray Drying: An Overview

Santos¹,

Maurício²,

Sencadas³

et al. 2018

Biomaterials - Physics and Chemistry - New Edition

125

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Spray drying is a well-known method of particle production which comprises the transformation of a fluid material into dried particles, taking advantage of a gaseous hot drying medium, with clear advantages for the fabrication of medical devices. In fact, it is quite common the production of microspheres and microcapsules designed for drug delivery systems. This review describes the different stages of the mechanism of the spray-drying process: atomization, droplet-to-particle conversion and particle collection. In particular, this work addresses the diversity of available atomizers, the drying kinetics and the importance of the configuration of the drying chamber, and the efficiency of the collection devices. The final properties of the dried products are influenced by a variety of factors, namely the spray dryer design, the feed characteristics and the processing parameters. The impact of those variables in optimizing both the spray-drying process and the synthesis of dried particles with desirable characteristics is discussed. The scalability of this manufacturing process in obtaining dried particles in submicron-to-micron scale favors a variety of applications within the food, chemical, polymeric, pharmaceutical, biotechnology and medical industries.

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Cospray Dried Antibiotics for Dry Powder Lung Delivery

Cited by 72 publications

References 30 publications

Microparticles for Inhalational Delivery of Antipseudomonal Antibiotics

Microparticles for Inhalational Delivery of Antipseudomonal Antibiotics

Formulation Optimization and Characterization of Spray Dried Microparticles for Inhalation Delivery of Doxycycline Hyclate

Spray Drying: An Overview

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