Multiscale Tomography: Probing The Nano-, Micro-, And Meso-Scale Resolution Of Inhalation Powder Structure

Understanding the agglomeration behavior of inhaled formulations is essential to ensure consistent aerosolization performance that maximizes drug deposition in the lower respiratory tract. Although many techniques are currently used to characterize critical material attributes (CMAs) such as the particle size distribution (PSD), these techniques suffer from low resolution, image in 2D projections, or are based on shape assumptions. Bearing in mind the importance of the powder microstructure, this work introduces the use of x-ray computed tomography (XCT) as a non- destructive, multiscale technique for characterizing inhalation formulations. Different grades of inhalation and tableting grade lactose have been analyzed using XCT, with distributions for size (volume weighted) and sphericity extracted and compared with laser diffraction and optical microscopy. The three-dimensional information provided from XCT provides a more accurate assessment of powder size and shape, demonstrating the promise for XCT as a valuable powder characterization technique that provides information about the powder microstructure, a descriptor now required from the U.S. Food and Drug Administration (Q3 equivalence).