Failure analysis of pharmaceutical products in any dosage form
Material analysis using TOF-SIMS in pharmacy: application examples
Pharmaceutical products exist in countless dosage forms: Tablets, capsules, coated tablets, powders, ointments, creams and plasters. Each of these products is subject to the strictest quality requirements due to the excipients and active ingredients they contain. Even the smallest traces of foreign material or impurities can impair their effectiveness. This can result in side effects or endanger the patient.
The cause of such impurities can be foreign contamination from manufacturing or packaging processes. Instrumental analysis is an indispensable tool for testing the chemical composition of pharmaceutical products. The choice of analytical methods is limited by different dosage forms, complex layer structures or the combination of different excipients and active ingredients. The TOF-SIMS method (time-of-flight secondary ion mass spectrometry) offers the possibility of precise material and damage analysis of pharmaceutical products
TOF-SIMS: Method for the analysis of pharmaceutical products
TOF-SIMS is a highly sensitive method in instrumental analysis. It enables the chemical characterization of pharmaceutical products down to the trace level. In addition to the detection of active ingredients, additives and fillers, the method enables the identification of contaminants. In addition, the layer structure (galenics) can be mapped – all without being restricted by the dosage form.
Problems/issues for dosage forms: Examples
- Plasters: What is the chemical composition of the outer layer?
- Nasal spray: Which active ingredients and additives can be chemically characterized?
- Pellets: What does the layer structure look like?
- Tablets: What is the chemical cause of the discoloration/staining on tablets?
- Eye drops: Can impurities be chemically identified?
- Ointment: What causes the discoloration?
- Coating: What is the chemical composition of the colored coatings?
- Injection solution: What is the chemical composition of the impurities?
- Atomizer: What is the chemical composition of the foreign particles?
- Suspension: What is the active ingredient composition of the pharmaceutical product?
The combination of a large number of excipients, fillers and active ingredients, as well as different dosage forms, can give rise to various quality assurance problems. Specific application examples include the contamination of citalopram tablets by zinc bromide.
Results and imaging of TOF-SIMS analysis of pharmaceutical products
In contrast to many other methods of instrumental analysis, TOF-SIMS is not limited to the chemical analysis of individual special substances and substance groups. Due to its high sensitivity, the TOF-SIMS method enables the identification of all species present. In addition, the method offers spatially resolved visualization of the detected chemical substances. Depending on the analysis objective, the data can be visualized as mass spectra or as spatially resolved images.
Case studies
Identification of the combination of active ingredients in a veterinary medicine
One advantage of the TOF-SIMS method for material analysis of pharmaceutical products is the identification of all substances contained in just one measurement. In this example, both active ingredients (paracetamol and meloxicam) contained in a veterinary medicine are detected.
TOF-SIMS imaging for spatially resolved material analysis
Galenics plays an important role in the efficacy of pharmaceutical products. With the help of imaging TOF-SIMS analysis (imaging), the layer structure of these products can be checked precisely and with high spatial resolution. The illustration shows the spatially resolved material analysis of an omeprazole preparation using a TOF-SIMS image.
Surface analysis of impurities in pharmaceutical products
The smallest impurities in pharmaceutical products, such as tablets, can impair their effectiveness. The TOF-SIMS method enables foreign contamination and foreign substances to be clearly identified. In the example below, zinc bromide was chemically identified as the cause of the dark spots, in addition to the active ingredient citalopram and excipients.
Identification of substances in the higher mass range
TOF-SIMS is also characterized by the fact that it is not subject to the typical limitations of many other methods. It enables the simultaneous analysis of elements or compounds of small and large masses. During the chemical analysis of a nasal spray, the active ingredient desmopressin and substances based on quaternary ammonium compounds (biocides) were detected.
Summary of results: TOF-SIMS for precise damage analysis and quality control
Precise chemical analyses using TOFSIMS down to the µm range enable the reliable identification of chemical substances. In this way, the cause of quality deviations such as impurities, discoloration, residues, foreign particles and other material defects can be found.
Contact us if you have any questions about the chemical composition and layer structure of your pharmaceutical products. We support you in troubleshooting and damage analysis as well as in monitoring the long-term stability (degradation) of your products. Our team will be happy to help you with any questions or problems you may have – also in other sectors.
