Multispectral imaging as a QA/QC tool

Multispectral imaging can measure colour, texture, gloss, shape and size to provide useful information on a finished pharma product, on the raw materials or on the manufacturing process. The technology offers rapid screening for out-of-specification tablets and contaminated powders; is suitable for the objective measurement of tablet defects; determines how well the ingredients of formulations are blended; and can be used to identify counterfeits through analysis of both packaging and product

Using Multispectral imaging in mixture analysis. Each component within the mixing process is assigned a weighting based on its spectral profile. The Mix value indicates to the operator the make-up of the sample from Powder A and Powder B

Imaging systems are becoming essential PAT and QA tools. Alan Bates and Tom Greenwell, Analytik, describe the applications for rapid multispectral imaging.

Multispectral imaging can unlock valuable information on both the quality and safety of pharmaceutical materials. Parameters measurable by the technique, such as colour, texture, gloss, shape and size, provide useful information on a finished product, on the raw materials or on the manufacturing process itself.

Multispectral imaging provides a rapid quality assessment of uniform and inhomogeneous samples alike by combining information on all of the above parameters automatically in just a few seconds, requiring no sample preparation and leaving the material intact.

The earliest applications for multispectral imaging were in the food industry as a replacement for subjective and expensive sensory panels. As these applications have become widespread, other highly regulated industries, such as pharmaceuticals, have begun to reap the benefits from multispectral imaging in ensuring high quality products, and as a weapon in the battle against counterfeiters.

The non-destructive investigation of materials with non-uniform colour and texture can be difficult, tedious and expensive. Conventional techniques such as NIR spectroscopy measure only a single point or average over a fixed area and do not give an objective overall assessment of visual quality. Multispectral imaging can be described as a trade-off, sacrificing some spectral resolution to increase spatial information and giving a ‘snapshot’ of the combined bulk properties of a sample, handling natural variation and inhomogeneity.

VideometerLab 2 successively strobes up to 20 wavelengths via LEDs, uniformly spaced around the inside of the integrating sphere, each generating a monochrome image

Traditional colour imaging uses three broad bands of colour – red, green and blue – and is known as RGB imaging. As a consequence of the broad bands, RGB imaging has very limited spectral resolution and is unsuited to differentiating samples showing variation within a single broad band.

Multispectral imaging refers to multiple wavelengths over the whole range from UV through visible to NIR (230 to 1050nm). VideometerLab 2, a lab-based multispectral imager from Danish company Videometer, is based on a high-intensity integrating sphere illumination, featuring light emitting diodes (LED) and a black and white high resolution (2056 x 2056 pixels) CCD camera. Measurements are combined at up to 20 different wavelengths into a single high resolution multispectral (2056 x 2056 x 20) image with every pixel in the image representing a spectrum. The schematic shows how internal reflection of the LEDs by the diffuse white inner surface of the sphere ensures diffuse homogeneous light for increased reproducibility, dynamic range, low scatter and shadow effects.

Schematic of integrating sphere. Internal reflection of the LEDs by the diffuse white inner surface of the sphere ensures diffuse homogeneous light for increased reproducibility, dynamic range, low scatter and shadow effects

The choice of illumination wavelength ensures each application can be optimised and is not restricted to the wavelengths spanned by traditional RGB technology. Using LEDs in the UV or NIR adds information not visible to the human eye. As an example, most objects are white or transparent in the NIR region, which allows for the separation of the colour and surface properties of the measured object. Uniform and non-uniform samples alike are simply placed in the target area and custom designed PC software for data capture and analysis means results are available in under 10 seconds, including sample handling time.

range of applications

Out of specification or contaminated product: Multispectral imaging offers a rapid solution to screening for out-of-specification tablets and contaminated pharmaceutical powders. Since the response of the test material is measured simultaneously at up to 20 different wavelengths, very subtle changes in composition can be detected and automatically flagged. This test is entirely non-destructive, requiring only a sub-sample of the product under test to be placed in a petri dish before analysis is carried out.

The technique is perfectly suitable for the objective measurement of tablet ‘Elegance’, a standard pharmaceutical test in which minor, major and critical defects are determined on a sub-sample, leading to acceptance or rejection of an entire batch. Tablet features inspected using multispectral imaging, both in the laboratory and on-line, include:

  • Shape integrity (no missing parts)
  • Tablet colour
  • Foreign material (impurities, spots)
  • Cracks
  • Dispenser colour and defects

RGB and pseudo images showing the identification of increased active ingredient within the formulation of a single tablet

Mixture Analysis: Understanding how well the ingredients of formulations are blended is critical across various stages of the production process. Multispectral imaging can be used to recognise different powders in single layer and bulk presentation. As a result, the success or otherwise of bulk mixing of two powders can be quantified.

RGB and pseudo images showing automatic discrimination between coated and uncoated mini-tabs that are visually identical. This allows the operator accurately to quantify the level and homogeneity of tablet coating

Counterfeit products: The presence of counterfeit products poses a serious hazard to human health. Multispectral imaging can be used to identify counterfeits through analysis of both packaging and product. Although visually it may be difficult to detect counterfeit packaging, it is a simple matter automatically to compare the shape and size of characters, trademarks, company names and logos on good/bad packaging. The use of specialised inks and texture effects on authentic packaging is simple to detect.

RGB and pseudo images of authentic (left) and counterfeit (right) pharmaceutical

Characterising the product itself is also straightforward. Subtle changes in size, shape, colour and markings can all be combined and used automatically to detect counterfeits, often without removing the product from the original blister packaging.

Multispectral imaging technology has the potential to become an important tool for measurements of non-homogeneous samples in the industry. High-performing and relatively inexpensive systems are available to provide accurate results in a broad range of critical applications.

RGB and Maximum Noise Function (MNF) transformed images of pharmaceutical powder highlighting dirt and dust contamination. MNF is the imaging equivalent of Principle Component Analysis (PCA)

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