Design, characterization, and aerosol dispersion performance modeling of advanced co-spray dried antibiotics with mannitol as respirable microparticles/nanoparticles for targeted pulmonary delivery as dry powder inhalers

Xiaojian Li, Frederick G. Vogt, Don Hayes, Heidi M. Mansour

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Dry powder inhalation aerosols of antibiotic drugs (a first-line aminoglycoside, tobramycin, and a first-line macrolide, azithromycin) and a sugar alcohol mucolytic agent (mannitol) as co-spray dried (co-SD) particles at various molar ratios of drug:mannitol were successfully produced by organic solution advanced co-spray drying from dilute solute concentration. These microparticulate/nanoparticulate aerosols consisting of various antibiotic drug:mannitol molar ratios were rationally designed with a narrow and unimodal primary particle size distribution, spherical particle shape, relatively smooth particle surface, and very low residual water content to minimize the interparticulate interactions and enhance in vitro aerosolization. These microparticulate/nanoparticulate inhalation powders were high-performing aerosols as reflected in the aerosol dispersion performance parameters of emitted dose, fine particle fraction (FPF), respirable fraction (RF), and mass median aerodynamic diameter (MMAD). The glass transition temperature (T g) values were significantly above room temperature, which indicated that the co-SD powders were all in the amorphous glassy state. The Tg values for co-SD tobramycin:mannitol powders were significantly lower than those for co-SD azithromycin:mannitol powders. The interplay between aerosol dispersion performance parameters and Tg was modeled where higher Tg values (i.e., more ordered glass) were correlated with higher values in FPF and RF and lower values in MMAD.

Original languageEnglish (US)
Pages (from-to)2937-2949
Number of pages13
JournalJournal of pharmaceutical sciences
Volume103
Issue number9
DOIs
StatePublished - Sep 2014

Keywords

  • aerosols
  • anti-infectives
  • confocal Raman microscopy
  • glass transition
  • lung
  • particle size respiratory delivery
  • pulmonary drug delivery
  • solid state particle engineering design
  • spray drying

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Design, characterization, and aerosol dispersion performance modeling of advanced co-spray dried antibiotics with mannitol as respirable microparticles/nanoparticles for targeted pulmonary delivery as dry powder inhalers'. Together they form a unique fingerprint.

  • Cite this