Article

Raman mapping to visualise the three-dimensional structure of pharmaceutical tablets

Raman mapping is a powerful tool that can be used to reveal details about the size and spatial arrangement of components throughout a tablet matrix. Here, Andrew Ewing, Don Clark and Fiona Clarke from the Materials Characterisation Team at Pfizer present a 3D imaging approach using Raman mapping to investigate pharmaceutical tablets.

The use of vibrational spectroscopy, including raman mapping, to study pharmaceutical products has been widely applied across the industry for several decades.1 Conventional vibrational spectroscopic approaches, namely Raman spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and near infrared (NIR) spectroscopy, are integral to providing chemical information about samples. The techniques reveal chemically specific information derived from vibrations within the molecules. These techniques can be utilised to understand polymorphs, intra- and inter-molecular interactions and solid form changes within pharmaceutical products. This knowledge can greatly impact formulation development and be used for troubleshooting applications.

Spectroscopic imaging and mapping offer label-free approaches to probe pharmaceutical tablets and visualise the identity of their components, spatial distributions, domain sizes and shapes”

The advent of spectroscopic, or chemical, mapping and imaging allows the spatial distribution of different components to be revealed by measuring the spectra within different areas of a sample. These spectroscopic imaging approaches have been employed in a range of pharmaceutical applications.2-7 The terms spectroscopic imaging and mapping are often used interchangeably in the literature: mapping acquires discrete spectra from single points via raster scanning across a sample on a movable stage; whereas, imaging acquires spectra in two spatial dimensions using an array detector. Chemical images are generated by plotting the absorbance of specific spectral bands across the measured area. Spectroscopic imaging and mapping offer label-free approaches to probe pharmaceutical tablets and visualise the identity of their components, spatial distributions, domain sizes and shapes.

The term ‘chemical imaging’ typically refers to spectra acquired from a two-dimensional (2D) array of a sample. A potential caveat of these methods is the assumption that the data acquired is representative of the sample bulk. However, it should be acknowledged that this is not always the case. A hypothetical system comprising spherical and cubic components can be used as an example.8 The point at which the sample is sliced (ie, cross‑sectioned) will affect the visualised diameter of the spherical component. Therefore, it is possible that the calculated diameter of the sphere will be underestimated. On the other hand, the cubic domains can result in over estimations of their domain sizes if they are sliced across one, or more, of their faces.

A pharmaceutical tablet is a 3D sample that comprises a mixture of components in which some are arranged as a network of agglomerated particles….2D imaging and mapping approaches may not provide a true representation of these networks throughout a tablet matrix”

A 2D chemical image probes a single layer of the sample, which is not always representative of the whole sample, particularly for 3D objects. A pharmaceutical tablet is a 3D sample that comprises a mixture of components in which some are arranged as a network of agglomerated particles. Processing of a blend (eg, granulation) and subsequent tableting can cause the powdered ingredients of a tablet to agglomerate. Therefore, 2D imaging and mapping approaches may not provide a true representation of these networks throughout a tablet matrix. It is widely accepted that the distribution of components throughout a tablet is important to ensure that reliable quality medicines are produced. Revealing information about this distribution can help to understand the effects of parameters like processing conditions during manufacturing processes. It would also provide opportunities to profile tablets that can be used as a baseline against subsequent batches produced, or for troubleshooting issue samples.

This article summarises some recent developments from the Materials Characterisation Team at Pfizer (Sandwich, UK) that has demonstrated a 3D imaging approach using Raman mapping to investigate pharmaceutical tablets.