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. Due to the excipients and active ingredients they contain, they are subject to the strictest quality requirements. The smallest impurities can impair efficacy, lead to undesirable side effects and jeopardize patient safety. 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 dosage forms, complex compositions and the combination of various excipients and active ingredients limit the choice of analytical methods. TOF-SIMS (Time-of-Flight Secondary Ion Mass Spectrometry) offers a precise way of analyzing the material and damage of pharmaceutical products.
TOF-SIMS: Method for the analysis of pharmaceutical products
TOF-SIMS is a highly sensitive method in instrumental analysis that enables the chemical analysis of pharmaceutical products down to the trace level. In addition to the detection of active ingredients, additives and fillers, the method enables the detection and identification of contaminations and the mapping of the layer structure (galenics) – 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 the use of different dosage forms, can lead to various problems in quality assurance. Specific application examples are, for example, the contamination of citalopram tablets by zinc bromide or the precise characterization of the layer structure of an omeprazole preparation.
Results and imaging of TOF-SIMS analysis of pharmaceutical products
Compared to many other methods of instrumental analysis, TOF-SIMS is not limited to the chemical analysis of individual special substances and substance groups. The high sensitivity of TOF-SIMS analysis enables the identification of all chemical species present, and a spatially resolved representation of the detected chemical substances is also possible. 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 active ingredients, excipients and fillers in one analysis. In this example, both active ingredients (paracetamol and meloxicam) are detected in a veterinary medicine.
TOF-SIMS imaging for spatially resolved material analysis
Galenics play an important role in the efficacy of pharmaceutical products. With the help of TOF-SIMS imaging analysis, the layer structure of these products can be tested 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 contaminants 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 almost all elements and compounds – both small and large masses. In the chemical analysis of a nasal spray, for example, 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.
