What do mapping and imaging techniques add to traditional spectroscopic analysis for pharmaceutical applications?
Janie Dubois
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With bulk or traditional single point spectroscopy, one spectrum is collected for each sample using a single element detector
with relatively short measurement times. For tablets, this provides one averaged measure of composition for either the whole
tablet or a selected portion. Mapping approaches and chemical imaging, on the other hand, record multiple spectra for each
sample, providing insight into the distribution of components — most usefully the API and key excipients — across the tablet's
surface.
Knowledge of the spatial location of different chemical components is valuable for a wide variety of applications, but is
particularly useful for the analysis of tablets because it enables manufacturers to understand the links between raw materials,
process parameters and a drug's critical quality attributes — the parameters that dictate clinical performance. By identifying
the physical distribution of chemical components within the tablet, mapping and imaging techniques allow an appreciation of
the relationship between structure and functionality. This helps with the more precise and sensitive definition of critical
quality attributes and with the development of understanding of how these can be effectively controlled during manufacture.
In this way, these systems closely support the knowledge-led approach enshrined in Quality by Design because they provide
the insight necessary to gain a more complete model of product behaviour.
Which applications require the extra spatial detail provided by imaging technology?
Assessing the information required for a particular application is crucial when selecting a spectroscopic system and the need
(or not) for spatial detail is key. While case by case consideration is advised, the following examples review some common
objectives and information goals.
Quality assurance and quality control
Quality assurance or control often requires only the average chemical composition of a tablet, together with perhaps, averaged
measures of moisture content and coating thickness. All of these can be estimated using bulk measurements. Mapping or imaging
is needed where spatial resolution is essential, for example in determining chemical and moisture distribution within a sample,
and/or coating uniformity. This is the case when distribution rather than just average composition critically impacts clinical
performance.
Troubleshooting/root cause analysis
For troubleshooting purposes, bulk measurements provide adequate information about chemical content (dosage) variation over
time in a manufacturing run or between batches, or to study differences in properties such as averaged coating thickness between
tablets. Spatial distribution information, on the other hand, can help to locate problems with coating integrity and thickness
variation across a tablet's surface or at the apex of angled tablets, for example, which may lead to dissolution test failures.
For more in-depth investigation, such as root cause analysis of dosage variation and the underlying reasons for a failed batch,
or batch-to-batch variability, spatially resolved measurements provide much more information and have become routine in many
companies. This application demands careful consideration of every piece of available information and is consequently an area
where imaging techniques have proven their value. Near-infrared chemical imaging, in particular, is favoured for troubleshooting
because the field of view of a single image can encompass a whole tablet surface, or even multiple tablets, which makes it
very fast and appropriate for the analysis of hundreds of tablets per day. This higher throughput is facilitated by automation
and is essential to obtain enough information to confidently make decisions about processes.
