title: NanoXCT: a novel technique to probe the internal architecture of pharmaceutical particles.
abstract: OBJECTIVE
  To demonstrate the novel application of nano X-ray computed tomography (NanoXCT) for visualizing and quantifying the internal structures of pharmaceutical particles.
  
  
  METHODS
  An Xradia NanoXCT-100, which produces ultra high-resolution and non-destructive imaging that can be reconstructed in three-dimensions (3D), was used to characterize several pharmaceutical particles. Depending on the particle size of the sample, NanoXCT was operated in Zernike Phase Contrast (ZPC) mode using either: 1) large field of view (LFOV), which has a two-dimensional (2D) spatial resolution of 172 nm; or 2) high resolution (HRES) that has a resolution of 43.7 nm. Various pharmaceutical particles with different physicochemical properties were investigated, including raw (2-hydroxypropyl)-beta-cyclodextrin (HβCD), poly (lactic-co-glycolic) acid (PLGA) microparticles, and spray-dried particles that included smooth and nanomatrix bovine serum albumin (BSA), lipid-based carriers, and mannitol.
  
  
  RESULTS
  Both raw HβCD and PLGA microparticles had a network of voids, whereas spray-dried smooth BSA and mannitol generally had a single void. Lipid-based carriers and nanomatrix BSA particles resulted in low quality images due to high noise-to-signal ratio. The quantitative capabilities of NanoXCT were also demonstrated where spray-dried mannitol was found to have an average void volume of 0.117 ± 0.247 μm(3) and average void-to-material percentage of 3.5%. The single PLGA particle had values of 1993 μm(3) and 59.3%, respectively.
  
  
  CONCLUSIONS
  This study reports the first series of non-destructive 3D visualizations of inhalable pharmaceutical particles. Overall, NanoXCT presents a powerful tool to dissect and observe the interior of pharmaceutical particles, including those of a respirable size.
authors.affiliation: Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Camperdown, NSW, 2006, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wong
authors.forename: Dexter
authors.initials: D
authors.lastname: D'Sa
authors.forename: Matthew
authors.initials: M
authors.lastname: Foley
authors.forename: John Gar Yan
authors.initials: JG
authors.lastname: Chan
authors.forename: Hak-Kim
authors.initials: HK
authors.lastname: Chan
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000280:Administration, Inhalation; D004337:Drug Carriers / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012710:Serum Albumin, Bovine / Q000737:chemistry; D059629:Signal-To-Noise Ratio; D013678:Technology, Pharmaceutical / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008055:Lipids; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D008353:Mannitol