Three-dimensional imaging of pharmaceutical tablets using serial sectioning and Raman chemical mapping

Carruthers, Hannah and Clark, Don and Clarke, Fiona and Faulds, Karen and Graham, Duncan (2022) Three-dimensional imaging of pharmaceutical tablets using serial sectioning and Raman chemical mapping. Journal of Raman Spectroscopy, 53 (6). pp. 1115-1125. ISSN 0377-0486 (

[thumbnail of Carruthers-etal-JRS-2022-Three-dimensional-imaging-of-pharmaceutical-tablets-using-serial-sectioning]
Text. Filename: Carruthers_etal_JRS_2022_Three_dimensional_imaging_of_pharmaceutical_tablets_using_serial_sectioning.pdf
Final Published Version
License: Creative Commons Attribution 4.0 logo

Download (1MB)| Preview


Chemical mapping by Raman spectroscopy is widely used in the pharmaceutical industry to characterise the distribution of components within pharmaceutical tablets; however, current methods do not go beyond examining an exposed surface area of a sample. There are known limitations with estimating domain size and shape statistics from 2D chemical images as the values obtained will depend on where the domain is sectioned, potentially under- or overestimating its true value. The combination of Raman spectroscopic mapping and serial sectioning has been recently explored as an alternative method to obtain a depth profile of a sample; however, to date, this has involved instrumentation capable of automated Raman mapping with subsequent sample sectioning. A key requirement for Raman mapping is producing an optically flat surface, and this becomes increasingly challenging for larger surface areas required for the examination of a pharmaceutical tablet. Here, we describe 3D imaging of a tablet matrix by combining Raman mapping with independent sample sectioning to provide appropriate lateral and axial resolution. The approach was first validated by analysing a spherical object of known size and shape and comparing the 3D domain size statistics calculated from the reconstructed image to its absolute values. The method was then applied to a three-component model system, simulating a pharmaceutical tablet, to determine the capability and applicability of the method for solid dosage formulations. The study demonstrated that relative differences in the size, shape and distribution of domains can be quantified enabling an enhanced understanding of the spatial arrangement of each component within the formulation and the effect of each processing condition on the final drug product. By visualising the 3D structure of a tablet matrix with demonstrable accuracy and precision using materials of known dimensions, new capabilities to enhance tablet manufacturing methods are now available.


Carruthers, Hannah ORCID logoORCID:, Clark, Don, Clarke, Fiona, Faulds, Karen ORCID logoORCID: and Graham, Duncan ORCID logoORCID:;