Advanced Imaging


Advanced Imaging Magazine

Updated: January 12th, 2011 10:01 AM CDT

What's In That Medicine?

Exploiting the wavelength interval between the visible and thermal infrared for chemical imaging in pharmaceutical sciences
Figure 1
© Malvern Instruments
Figure 1: False-color NIR chemical image of similar pharmaceutical tablets produced by different manufacturers.
Figure 2
© Malvern Instruments
Figure 2: Visible and NIR chemical image of an adulterated blister pack of pharmaceutical tablets.
Figure 3
© Malvern Instruments
Figure 3: False-color NIR chemical image of a tablet, where the active pharmaceutical ingredient (shown in red) is not distributed evenly across the tablet.

By Janie Dubois, Ph.D., and E. Neil Lewis, Ph.D., Malvern Instruments

Digital imaging in the visible (400 to 700 nm) spectral region now is commonplace with the availability of low-cost CCD and CMOS cameras and powerful data processing hardware and software. In machine vision, for example, it is used for product inspection, quality control, quality assurance and manufacturing automation.

More recently, infrared cameras traditionally used for thermal imaging or night vision applications (3,000 to 5,000 nm) also have gained acceptance as valuable productivity tools in a number of industries and, in most cases, the data processing software is common to both imaging modalities. The two approaches may reasonably be labeled as broadband imaging because the light in both spectral intervals is integrated into a single image frame typically recorded at video frame rates. A less well-developed and commercially exploited region lies between 1,000 and 2,500 nm. In this spectral interval, many molecular species absorb energy which can be utilized to generate image contrast that is chemically specific. A variety of camera technologies—cooled and uncooled—operates in this spectral interval and, when combined with a narrow-band wavelength selection device, provides high-speed chemical imaging capability. The approach was originally deployed for remote sensing applications and termed hyperspectral imaging, but more recently has found its way into a variety of industrial applications; in this capacity, it generally is referred to as near infrared chemical imaging (NIRCI). Indium Antimonide (InSb), Indium Gallium Arsenide (InGaAs) and Mercury Cadmium Telluride (MCT) cameras typically are used for chemical imaging in this spectral range.

While NIRCI imaging is becoming more broadly utilized in industry, one of the more exciting application areas is the pharmaceutical industry1. Recent trends in the industry to improve manufacturing efficiency, reformulate existing products, combat counterfeiting and develop ever more complex drug delivery systems are making the industry acutely aware of the need for increasingly sophisticated analytical instrumentation. In this regard, the pharmaceutical industry has adopted NIRCI as a technology that can provide such information.


The vast majority of pharmaceutical products are delivered in what are called solid-dosage forms, or tablets. A typical product contains one or more active ingredients as well as a number of excipients or non-active ingredients. In even the simplest product, there is a non-uniform distribution of these components that can exist at the micro (less than 100 µm) or macro (greater than 100 µm) scales. In many cases, this chemical heterogeneity is not problematic, but depending on the product and perhaps the potency of the active ingredient, it can lead to problems with uniform dosage strength or potency. In other situations, variations in the particle or domain size of the product components also can lead to problems with the drug delivery process by impacting dissolution or solubility of the drug when ingested. For more complicated formulations that involve sustained release mechanisms, the need to fully understand and control this chemical heterogeneity becomes imperative to the performance of the device.

In its simplest form NIRCI provides the ability to qualitatively visualize the spatial distribution of the various chemical species in finished pharmaceutical products and their intermediates. In practice, it provides much more quantitative information. Data pertaining to the potency and purity of a particular product as well as critical information about the presence of chemical gradients or non-uniform chemical distributions is all available from a single measurement. In addition, domain sizes for all the components in the mixture, as well as information on coating thickness uniformity, can be derived directly from measurements of the chemical images. As such, the approach now is seen as an important step in the goal of pharmaceutical manufacturers to improve manufacturing quality and to reduce manufacturing failures.

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