Measuring the Particle Packing of l-Glutamic Acid Crystals through X-ray Computed Tomography for Understanding Powder Flow and Consolidation Behavior

Abstract

The morphology of free-flowed and gravity consolidated crystal powder beds of the alpha and beta polymorphic forms of L-glutamic acid, together with a detailed analysis of particle density and microstructure within alpha form tablets using state -of-the-art X-ray computed tomography (XCT), is presented. The Carr's index is measured to be 19.7 and 35.2 for the bulk powders of the prismatic alpha form and needle-like beta form, respectively, revealing the alpha forms increased powder flowability versus the beta form. XCT reveals the alpha form consolidates under gravity more efficiently than beta, where the final measured bed density of the alpha form is 0.724 g/cm 3 compared to 0.248 g/cm 3 for the beta form, which is found to be caused by the inability of the beta particles to pack efficiently along their needle axis. Tabletting studies reveal that the alpha form consolidates into compacts of intermediate tensile strength, whereas the beta form cannot be compacted under these conditions. XCT analysis of tablets formed from α-form crystals reveals two discrete density regimes, one low-density region of fine powder which accounts for 53.8% of the compact, and highdensity regions of largely intact single crystals which account for 44.2% of the compact. Further analysis of the tablet microstructure reveals that the crystal particles are generally orientated with their basal {0 0 1} plane, normal to the compaction force and that small microcracks which appear within the particles generally occur perpendicular to the surface and are orientated through possible {1 1 0} and {1 0 1} fracture planes. XCT also reveals evidence for incipient transformation between the meta-stable alpha to stable beta phase at concentrations below that detected using laboratory X-ray diffraction. The results show that XCT can accurately measure the extent of tapping induced densification and reveals the powder bed mesostructure characteristics and tablet microstructure for the two polymorphic forms of alpha and beta L-glutamic acid.

WITHDRAWN: 3D characterisation of dry powder inhaler formulations: Developing X-ray micro computed tomography approaches

“…A simple compressibility index such as Carr's index or Hausner ratio gives no insight on particle organisation, and although flow function coefficient curves provide a relation between particle size, shape and flowability, they too do not allow the flow behaviour to be visualised at the particle level. The proof of concept experiments demonstrate how XCT allows such visualisation, also providing information on particle interconnectivity, and whether particle orientations also change during tapping [67]. Scans would need to be optimised for image resolution rather than speed, and a more systematic tapping or flowing mechanism synchronised with the XCT machine would allow motion between taps to be resolved [17].…”

On the Breakage of High Aspect Ratio Crystals in Filter Beds under Continuous Percolation

“…From a material science point of view, breakage across the needle axes involves breaking hydrogen-bonds (LGA, ( 22 )), van der Waals forces (Ibuprofen, ( 23 )) and pi-pi interactions (PABA, ( 24 )). Our initial premise was that the nature of the bonding of molecules in their lattice correlates with the breakage strength.…”

“…The volumes were smoothed using a bilateral filter and the voidage fraction ( ε ) was calculated for each virtual cross-sectional slice of the 3D volume using a method adapted from ( 22 ), i.e. 1 minus the ratio between the area occupied by the powder and the total analysis area.…”

“…From a material science point of view, these three materials have lattices that require breaking of very different inter molecular forces. Breakage across the needle axes involves breaking singular H-bonds (LGA, ( 22 )), van der Waals forces (ibuprofen, ( 23 )) and pi-pi interactions (PABA, ( 24 )). Our premise is that the varying intermolecular forces result in significantly different breakage strength and behaviour on compression of the particles under liquid percolation.…”

Crystallographic tomography and molecular modelling of structured organic polycrystalline powders

“…X-ray computed tomography (CT) is a non-destructive X-ray microscopy (XRM) technique [19][20][21] capable of 3D imaging of particle morphology 22 and powder micromeritic properties, 23 but providing no direct chemical or crystallographic information. 24 X-ray diffraction (XRD) methods on the other hand are routinely used to analyze crystal structure and different chemical phases within a sample, but are unable to give any precise characterisation of the spatial orientations and relative positions of microparticles within a bulk powder bed. Consequently, a number of diffraction tomographies have evolved to enable 3D mapping of crystalline structures.…”