NanoXCT: a novel technique to probe the internal architecture of pharmaceutical particles.

Abstract

To demonstrate the novel application of nano X-ray computed tomography (NanoXCT) for visualizing and quantifying the internal structures of pharmaceutical particles. 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. 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. 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.