Microspectroscopic Failure Analysis

  • Connect

Pharmaceuticals

Identify Particles and Inclusions.

Automotive

Analyze Defective Car Parts.

Paper

Examine Inhomogeneity.

Effective Failure Analysis

Determine the Chemical Reason Behind Product Failure.

Polymer and Plastic Products

Detect Wrong Composition, Identify Contamination.

Electronics

Determine Contamination.

Failure Analysis
in Pharmaceutical Products

The detection and search for the cause of product failures in pharmaceutical substances is especially important since these types of defects are potentially harmful to the patient. Thus, pharmaceutical products are highly regulated and defects are not tolerable.

To prevent mix-up of components in the manufacturing process IR and Raman spectroscopy are widely used by pharmaceutical manufacturers for verifying the correct identity of incoming raw materials. In failure analysis, FTIR and Raman microscopy are ideally suited to determine the chemical nature and the origin of all kinds of particles, inclusions and other microscopic contaminations.

Raman microscopy even allows to measure inside of closed transparent containers and within water based formulations without the need to isolate the particles.

  • Identification of particles

  • Determination of inclusions

  • Homogeneity of tablets

Determination of Inclusions

Example: Chemical identification of an inclusion in a tablet Pharmaceutical tablets have to be free from inclusions. If an inclusion is detected e.g. by visual inspection its chemical nature has to be determined to raise the chances finding its origin. The figure below shows a white tablet with a yellow spot inside. To discriminate the inclusion from the general matrix of the tablet a series of positions was measured on the yellow spot and next to it. Using the fully automated ATR (Attenuated Total Reflectance) mode of the LUMOS the region of interest was analyzed without any sample preparation.

The next figure shows the visual microscopic image of the inclusion inside the tablet together with the measurement positions. The spectra are colored according to their position. It is obvious that the spectra measured on the inclusion (blue) have a much different signature than the ones on the general matrix of the tablet (red). By searching a digital spectra data base the chemical identity of the inclusion was identified as stearate.

click to enlarge

Read Application Note M119 about microanalytical pharma applications.

Identification of Particles

Particles in liquid pharmaceutical formulations are a potential health risk for patients. Therefore, great care is taken to avoid particle formation in the first place. Any detected particles are analyzed thoroughly to find and remove the reason for their appearance.

FTIR microscopy is a powerful technique to determine the chemical identity even of individual particles. Before the IR analysis, the particles have to be isolated, washed and dried in order to perform a reliable spectroscopic analysis. As an example, the image below shows particles isolated on a gold filter.

Confocal Raman microscopy even provides the option to analyze such a particle directly inside vials or syringes without any sample preparation.

click to enlarge

Read Aplication Note AN M105 about the IR microscopic identification of particles and inclusions.
See example about non-invasive particle identification using confocal Raman microscopy in our Application Note AN R527.

Homogeneity of Tablets

Example: Distribution of API´s and excipients determined by Raman imaging Tablets are often complex mixtures of active pharmaceutical ingredients (API), fillers and excipients. Knowledge about the distribution of the single ingredients can help to improve product quality and to detect improperly mixed tablets. The image below shows a high resolution Raman image of a painkiller tablet. It visualizes the distribution of 3 different API’s: Caffeine (green), acetyl salicylic acid (blue) and paracetamol (red) on top of the visual microscopic image. Altogether, 100x100 single spectra were measured in less than 5 minutes.


Further Information

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