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Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery

Authors Duan J, Vogt FG, Li X, Hayes D Jr, Mansour HM

Received 18 May 2013

Accepted for publication 1 August 2013

Published 17 September 2013 Volume 2013:8(1) Pages 3489—3505

DOI https://doi.org/10.2147/IJN.S48631

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Jinghua Duan,1,2 Frederick G Vogt,3 Xiaojian Li,1 Don Hayes Jr,4,5 Heidi M Mansour6

1University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences – Drug Development Division, Lexington, KY, USA; 2University of Washington-Seattle, College of Pharmacy, Department of Pharmaceutics, Seattle, WA, USA; 3GlaxoSmithKline, Analytical Sciences, Product Development, King of Prussia, PA, USA; 4The Ohio State University College of Medicine, Departments of Pediatrics and Internal Medicine, Nationwide Children's Hospital Lung and Heart-Lung Transplant Programs, Columbus, OH, USA; 5The Ohio State University, Davis Heart and Lung Research Institute, Columbus, OH, USA; 6The University of Arizona–Tucson, College of Pharmacy, Skaggs Center of Pharmaceutical Sciences, Tucson, AZ, USA

Abstract: The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders.

Keywords: lung infection, respiratory, lung surfactant, solid-state particle engineering design, aerosol, fluoroquinolone antibiotic drug delivery

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