Industrial Process Tomography - Platform II grant funded by EPSRC

FACULTY OF ENGINEERING

 

Colloid Vibration Potential Imaging

X-ray micro-tomography - shape and orientation of single crystals

There is considerable interest in identifying the particular components of crystal faces for powders of pharmaceutical ingredients given that they probably play an important role in downstream unit processes. Previously, identification of the molecular composition of particular faces was restricted to large single crystals, as part of the drug registration process [1],[2]. This information is now needed in a more applied sense. Knowing the specific molecular nature of a particular face allows the important physico-pharmaceutical properties that stem from this to be better understood [3]. This includes its wettability, surface adhesive properties; and the likely
fragmentation and compaction behaviour.

Recent development in high throughput methodology and instrumentation has brought about a significant change in approach within the pharmaceutical industry [4]. This presents an opportunity to assess the feasibility of simultaneous micro-tomographic shape analysis and X-ray
diffraction molecular orientation determination on single, micro-crystals. This arises because of the capability available at the new Diamond beamline, which can make such measurements down to a 5 μm beam size. In principle it becomes possible to determine molecular orientation at a very small level of size – possibly as low as 2 μm. When coupled with X-ray based micro-tomography conducted on identical crystals, the shape and olecular
orientation can be determined for surfaces of realistically sized small particles [5].

This will allow the investigation of a range of pharmaceutical secondary processes, such as milling, fluid energy milling (micronisation), and granulation. Furthermore it offers the chance to study mixing and agglomeration / deagglomeration at a molecular level.

 


(a)

1b(b)

1b
 
X ray diffraction
(c)
X ray diffraction
(d)
(e)


 

Figure 1 (a) - (e)  Photographs (left) at two different positions (a), (b) and the corresponding X-ray diffraction patterns (c), (d) of the small aspirin crystal (shown in red circle) on a large crystal. These photographs were captured during the experiment when the crystal was rotated to 1800 at 30 oscillations. The photograph (e) is a close-up of the one in the middle.

Author Information: Kevin Roberts, Institute of Particle Science and Engineering, School of Process, Environmental and Materials Engineering, Email: k.j.roberts@leeds.ac.uk

References:

  1. Byrn, S., Pfeiffer, R., Ganey, M., Hoiberg, C., Poochikian, G., (1995). 'Pharmaceutical Solids: A Strategic Approach to Regulatory Considerations'. Pharmaceutical Research, 12 ((7)):945 -954.
  2. York, P., (1983). 'Solid-state properties of powders in the formulation and processing of solid dosage forms'. International Journal of Pharmaceutics, 14:1-28.
  3. Muster, T.H. and Prestidge, C.A., (2002). 'Face specific surface properties of pharmaceutical crystals'. J Pharm Sci, 91 (6):1432-1444.
  4. FDA, (2004). 'Pharmaceutical cGMPs for the 21st century : A Risk based approach'.
  5. Ramachandran, V., Armour, W., Evans, G., Roberts K.J., et al “Characterisation of micro particulates using a novel technique combining high resolution X-ray Micro-Tomography and X-ray Diffraction at the Diamond Light Source” submitted to the 6th World Congress on Process Tomography, Beijing, September 2010.