Pharmaceuticals are subject to the strictest controls – and rightly so. International and regional regulators work to mandate the highest quality standards for therapeutics and medical devices, which puts a real burden of responsibility on manufacturers and packagers.
Innovative quality control and quality assurance processes are required to guarantee that dosage form products are fit for market circulation. This includes testing for the presence of particulates and residue and identifying these contaminant elements to determine their genesis.
Detecting particulates and residues in pharmaceuticals is the first step in characterizing the contaminant and eliminating the contamination source. Numerous analytical techniques are used to identify impurities in dosage form pharmaceuticals, including scanning electron microscopy coupled with energy dispersive x-ray (SEM-EDX) and Fourier transform infrared (FTIR-) microscopy.
This blog post will explore the use of each technique for detecting and identifying particulates and residue in pharmaceuticals in further detail.
Outlining SEM-EDX for Particulates and Residue Analysis
SEM-EDX is a powerful microscopic technique used to generate high-resolution 3D maps of a sample’s topography and its elemental composition. This is achieved using a fine-tuned electron source that bombards the sample in high vacuum conditions. Secondary and backscattered electrons are produced by this energetic collision, as well as elementally-characteristic x-rays. The intensity of reflected secondary electrons is generally determined by the surface topography of the sample. In an SEM-EDX microscope, sensitive photo-detectors are used to acquire both the emitted secondary electrons and x-rays to quantitatively generate detailed imagery about the physiochemical characteristics of a pharmaceutical sample.
With magnifications of up to 50,000x and detection limits of between 1000 – 3000 parts per million (ppm), SEM-EDX can be used to detect particulates and residue in both broad phases and local impurities.
Particulates and Residue Analysis with FTIR-Microscopy
FTIR-microscopy isolates a sample within an interferometer equipped with a highly-tuned infrared light source. The sample absorbs incident IR waves and the microscope acquires the intensity and wavelength of this absorbed spectra to identify the functional groups present in the sample. This can be used to detect particulates and residue at extremely small localities, with a minimum IR spot size of 10 – 15 micrometers (µm).
Applying these Techniques to Pharmaceuticals
These analytical methods are important for pharmaceutical quality control and assurance due to their high-precision and reliability. Scientists can test for chemical and physical variations at extremely high resolution, allowing identification of contaminants via their distinct elemental signatures. Identified particulates and residues can then be used to detect sources of contamination in the production chain and eliminate the generation of similar impurities in future batches.
For example, Jordi Labs used SEM-EDX and FTIR-microscopy to identify brown particles observed in a bioreactor using their distinct infrared and x-ray spectra. Each was able to determine the major trace elements as iron (Fe), oxygen (O), and nickel (Ni) to quantitatively characterize the contaminant as rust and prove that the bioreactor was beginning to degrade.
Corroding metals and fluoropolymer gaskets are one of the primary sources of particulate and residue contamination of pharmaceutical products, resulting in the deposition of harmful small molecule substances onto raw pharmaceutical ingredients. If these elements go undetected, they can cause significant health problems and result in the loss of FDA approval.
Particulate and Residue Analysis with Jordi Labs
Jordi Labs specializes in particulate and residue analysis for pharmaceutical products, providing a robust service designed to detect and identify contaminants in end products or raw materials to eliminate impurities from the manufacturing process and supply chain.
If you would like any more information, read our primer on Particulates and Residue Analysis with Jordi Labs. Or, if you would like to speak with us about a particular application, simply contact us directly.