Developing and advancing dry powder inhalation towards enhanced therapeutics

Stegemann, Sven; Kopp, Sabine; Borchard, Gerrit; Shah, Vinod P.; Şenel, Sevda; Dubey, Rajesh Kumar; Urbanetz, Nora Anne; Cittero, M.; Schoubben, Aurelie Marie Madeleine; Hippchen, C.; Cadé, Dominique; Fuglsang, Anders; Morais, José; Borgström, Lars; Farshi, F. S.; Seyfang, Karlheinz; Hermann, Róbert; Putte, A. van de; Klebovich, Imre; Hıncal, A. A.

doi:10.1016/j.ejps.2012.10.021

Cited by 61 publications

(19 citation statements)

References 98 publications

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“…In this study, we have demonstrated that the addition of HIS to the spray-drying solution can generate powders with high condensability, through enhancing the distance between particles, leading to decreased cohesion between particles with subsequent increased dispersibility and improved deposition in the lungs. Furthermore, the use of LUE was shown to increase the flowability, dispersibility and aerosolization performance of drug particles for inhalation, as reported in previous studies [8,12,15,23,24]. The mechanism was probably related to its hydrophobic feature [25] and surfactant-like facet [26], which may facilitate the LEU molecules drift to the droplet surface during spray-drying and therefore modify surface characteristics, in particular the aerosolization characteristics.…”

Section: In-vitro Aerosolization and Depositionmentioning

confidence: 74%

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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Section: In-vitro Aerosolization and Depositionmentioning

confidence: 74%

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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“…Polyethylene glycol (PEG)-coated nanoparticles have been shown to significantly improve the mucus penetration of various therapeutics encapsulated in NP due to the formulation size, PEG coating, and protection of active pharmaceutical ingredients (39). Unfortunately, aerosolized nanoparticles will be exhaled owing to their small size and mass and while aerosolized particles with aerodynamic diameters of 1–5 µm can deposit into the deep lung region, which limits their efficacy for targeting the infection site in mucus as aerosol drug delivery vehicles (40, 41). …”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Nanocomposite Microparticles (nCmP) for the Treatment of Cystic Fibrosis-Related Infections

Wang

Meenach

2016

Pharm Res

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Purpose Pulmonary antibiotic delivery is recommended as maintenance therapy for cystic fibrosis (CF) patients who experience chronic infections. However, abnormally thick and sticky mucus present in the respiratory tract of CF patients impairs mucus penetration and limits the efficacy of inhaled antibiotics. To overcome the obstacles of pulmonary antibiotic delivery, we have developed nanocomposite microparticles (nCmP) for the inhalation application of antibiotics in the form of dry powder aerosols. Methods Azithromycin-loaded and rapamycin-loaded polymeric nanoparticles (NP) were prepared via nanoprecipitation and nCmP were prepared by spray drying and the physicochemical characteristics were evaluated. Results The nanoparticles were 200 nm in diameter both before loading into and after redispersion from nCmP. The NP exhibited smooth, spherical morphology and the nCmP were corrugated spheres about 1 µm in diameter. Both drugs were successfully encapsulated into the NP and were released in a sustained manner. The NP were successfully loaded into nCmP with favorable encapsulation efficacy. All materials were stable at manufacturing and storage conditions and nCmP were in an amorphous state after spray drying. nCmP demonstrated desirable aerosol dispersion characteristics, allowing them to deposit into the deep lung regions for effective drug delivery. Conclusions The described nCmP have the potential to overcome mucus-limited pulmonary delivery of antibiotics.

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“…Furthermore, crystalline and amorphous materials distributed at the surface of pharmaceutical powder particles affect how particles interact with each other 6 , which in turn alters the powder behavior during aggregation or dispersion [6][7][8] . While the quantification of amorphouscrystalline materials has been investigated by numerous nonspatially resolved techniques [9][10][11] , spatial distribution is considerably more challenging to assess at the surface of materials.…”

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confidence: 99%

Imaging of Crystalline and Amorphous Surface Regions Using Time-of-Flight Secondary-Ion Mass Spectrometry (ToF-SIMS): Application to Pharmaceutical Materials

et al. 2016

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. (2016) Imaging of crystalline and amorphous surface regions using time-of-flight secondary-ion mass spectrometry (ToF-SIMS): application to pharmaceutical materials. Analytical Chemistry, 88 . pp. 3481-3487. ISSN 1520-6882 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/32837/1/Manuscript%20File_Deea%27s%20version %5B2%5D.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the University of Nottingham End User licence and may be reused according to the conditions of the licence. For more details see: http://eprints.nottingham.ac.uk/end_user_agreement.pdf A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. ABSTRACT:The structure of a material, in particular the extremes of crystalline and amorphous forms, significantly impacts material performance in numerous sectors such as semiconductors, energy storage and, in the subject of this paper, pharmaceutical products. To characterize the spatial distribution for crystalline-amorphous forms at the uppermost molecular surface layer, we performed time-of-flight secondary-ion mass spectroscopy (ToF-SIMS) measurements for quench-cooled amorphous and recrystallized samples of the drugs indomethacin, felodipine and acetaminophen. Polarized light microscopy was used to localize crystallinity induced in the samples under controlled conditions. Principal component analysis was used to identify the subtle changes in the ToF-SIMS spectra indicative of the amorphous and crystalline forms for each drug. The indicators of amorphous and crystalline surfaces were common in type across the three drugs, and could be explained in general terms of crystal packing and intermolecular bonding, leading to intramolecular chain scission in the formation of secondary ions. Less intramolecular scission occurred in the amorphous form, resulting in a greater intensity of molecular and dimer secondary ions. To test the generality of amorphous-crystalline differentiation using ToF-SIMS, a different recrystallization method was investigated where acetaminophen single crystals were recrystallized from supersaturated solutions. The findings indicated that the ability to assign the crystalline/amorphous state of the sample using ToF-SIMS was insensitive to the recrystallization method. This demonstrates ToF-SIMS capabilities of detecting and mapping ordered crystalline and disordered amorphous molecular materials forms at micron spatial resolution in the uppermost surface of a material.

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Developing and advancing dry powder inhalation towards enhanced therapeutics

Cited by 61 publications

References 98 publications

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

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

Synthesis and Characterization of Nanocomposite Microparticles (nCmP) for the Treatment of Cystic Fibrosis-Related Infections

Imaging of Crystalline and Amorphous Surface Regions Using Time-of-Flight Secondary-Ion Mass Spectrometry (ToF-SIMS): Application to Pharmaceutical Materials

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