When and why should the pharmaceutical industry use NIR

NIR chemical imaging is based on the same principles as NIR spectroscopy, but uses a focal plane array detector in place of a single detector element to capture the spectral signature at tens of thousands of spatially resolved positions simultaneously. Some have called it NIR spectroscopy on steroids! The parallel data acquisition results in a very high throughput; one image takes under 3 minutes to acquire, which corresponds to 2 milliseconds per full spectrum. For certain quality control applications, such as monitoring the spatial distribution of an API for example, it is possible to acquire the spectral information at a few selected wavelengths. In the latter case, all spatial positions are interrogated in a few seconds, which means that hundreds to thousands of discrete samples can be imaged in a day.

The main difference between NIR chemical imaging and traditional NIR spectroscopy is the dimensionality of the measurement, which relates to the purpose of the measurement. Traditional NIR spectroscopy is an averaging technique; a single spectrum is acquired from a fairly large spot and possibly all the way through a tablet. This spectrum represents the average chemical composition of the tablet and is very powerful to determine the concentrations of various organic ingredients. NIR chemical imaging is a detail-oriented technique; a multitude of spectra are acquired, each from a very small spot on the tablet and from a limited depth. Each spectrum represents the chemical composition of a small area, which enables the comparison of all the spots acquired to determine the spatial distribution of various ingredients within one tablet. This spatial distribution is then compared amongst samples and correlated with performance parameters such as dissolution rate and stability.

When should it be used?
NIR chemical imaging is a very powerful tool for the analysis of coated and uncoated pharmaceutical tablets, granules, extrusion cores and transdermal delivery systems. The key is always to aim for an application where it is the chemical heterogeneity present within the sample that is important. Chemical heterogeneity can be deliberate and part of the structure that yields the desired performance, or it may be caused by process changes and negatively impact performance. Such applications abound in various steps of formulation design, analytical services and quality control. Examples include the determination of blending, coating or milling end‑points in formulation design, risk assessment of ingredient selection and changes of suppliers, troubleshooting of dissolution failure, and counterfeit detection and sourcing. If the analysis seeks a comparison of means (for example dose uniformity between tablets), traditional NIR spectroscopy is more appropriate.

Most analyses performed with NIR chemical imaging on solid dosage forms are done in diffuse reflectance — a sampling technique that simply involves positioning a tablet or other sample on the sample stage and “staring” at it with the camera for a few seconds to a couple of minutes. The main advantage of using diffuse reflectance in NIR imaging with a system providing a wide depth of field is the absence of sample preparation, which increases analysis speed and decreases personnel involvement (and associated cost). Finally, NIR chemical imaging is a great tool for Quality by Design (QbD), laboratory analysis and even at-line measurements, but generally overkill for on-line monitoring. The technology exists to perform blend monitoring on line and automation in data analysis can be implemented, but experience has revealed that it generates an amount of data that often needs to be distilled down to become manageable, to a point that makes it only marginally more informative than a single point, traditional NIR on-line probe would have been. The cost of on-line implementation is also an important consideration. Also, NIR chemical imaging is better suited for solid samples; powders with a particle size in the single or tens of microns range are better interrogated by a particle imaging system. Such systems can rapidly sort through tens of thousands of particles to find the ones of interest based on size and shape; chemical analysis with a spectroscopic approach can then be more efficiently performed strictly for these selected particles.

How does the industry benefit?
Better understanding of processes and products leads to better control, a smaller regulatory burden when the time comes to implement changes and better profitability. In this regard, NIR chemical imaging is fully aligned with the QbD initiative and provides information that bridges the gap between starting material quality assurance and performance verification of finished tablets, transdermal patches and oral wafers. In addition, the ability to analyse intermediates enables the gathering of a knowledge base on the effects of ingredients and modifications at various stages of the process during formulation development, and further link into the consequences for finished products. In short, NIR chemical imaging is a risk assessment tool that provides quantitative data for the determination of critical quality attributes.

The knowledge gathered during formulation development can save a lot of time and money when having to deal with a performance failure. However, even when it is not used to collect this important information during formulation development, NIR chemical imaging remains a powerful tool for root-cause analysis of performance failure of finished products and intermediates, enabling the rapid implementation of corrective measures. As such, it can have a significant impact on production efficiency and cost.The power and limitations of NIR chemical imaging are quite well-understood at this point and the technology already available will satisfy measurement needs. We believe that NIR chemical imaging-derived information will be increasingly requested for new product applications because of the fact that it bridges a gap in product and process understanding that is important for the success of QbD. As more applications include the technical data acquired with this instrumentation, there will be less acceptance of the old gaps in knowledge and assumptions.

The Future
Automation of both data acquisition and processing will definitely see the most innovations over the next decade as the technique moves into routine measurements for formulation development and quality assurance. It will become more of a “walk-up” instrument, utilised by non-spectroscopists and providing a numerical, or even a pass/fail type of answer. Standard operating procedures and validated methods will be key to routine deployment, especially to address the needs of ever-shrinking analytical laboratory staff in many pharmaceutical companies.

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