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

Abstract

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.

Innovative Approaches for Drug Discovery: Quantifying Drug Distribution and Response with Raman Imaging

“…195 Serial sample sectioning and image reconstruction have been used to achieve 3D volumetric mapping of tablets with Raman imaging. 196 Spatially offset Raman spectroscopy (SORS) or transmission Raman spectroscopy has also been integrated into pharmaceutical studies to address the penetration depth issue at the expense of spatial resolution. The accuracy of carbamazepine polymorph and cocrystal quantification with transmission geometry notably exceeded that of the conventional backscattering modality.…”

Data processing of three-dimensional vibrational spectroscopic chemical images for pharmaceutical applications

“…This case study showcases the data processing methods discussed above using a real Raman dataset that we published in the Journal of Raman Spectroscopy. 11 The 3D data processing workflow is documented in Figure 4.…”

“…10 Recently, the combination of spectroscopic mapping with serial sectioning has enabled full visualisation of the three-dimensional (3D) microstructure of a tablet system to be achieved. 11 A 3D dataset can be reconstructed by stacking individual 2D chemical images collected at regular depth intervals into the sample. To further enhance the added value of 3D spectroscopic mapping methods, this paper outlines the methods required to visualise, process and analyse 3D volumetric data for pharmaceutical applications.…”

“…The 3D data processing workflow for an example 3D Raman dataset. The example dataset was research we previously published in the Journal of Raman Spectroscopy 11.…”

Evaluation of laser direct infrared imaging for rapid analysis of pharmaceutical tablets

“…9 Recently, the combination of Raman chemical imaging with serial sectioning has enabled full visualisation of the three-dimensional (3D) microstructure of a tablet system. 10 The applicability of this method is limited by the data collection time required to obtain high-denition two-dimensional (2D) chemical images of the exposed surface. To overcome the limitations of current vibrational spectroscopic chemical imaging techniques, this study assesses the capabilities of novel laser direct infrared (LDIR) chemical imaging that offers the opportunity of obtaining high-denition chemical images of the sample surface at an order of magnitude faster.…”