Near-infrared spectroscopy (NIRS) offers numerous advantages over many wet-chemical analytical methods, including the ability to determine a diverse range of parameters simultaneously. Near-infrared spectroscopy is economical and fast, enabling qualitative and quantitative analyses that are noninvasive and nondestructive.
An indispensable analysis technique, NIRS can be used along the entire production chain – from incoming materials to processing, and on to the quality control of finish products (Figure 1). Near-infrared spectroscopy also meets the requirements of numerous international pharmacopoeias, e.g., USP, Ph. Eur., and JP.
Applications of NIRS along the production chain
INTERACTION OF LIGHT AND MATTER
Molecular vibrations are induced in the near-infrared region of the magnetic spectrum (800–2500 nm) – i.e., from the end of the visible to the mid-infrared (MIR) range. The main absorption bands of the functional groups of chemical substances are located in the MIR range and are very strong. The absorption bands of the harmonics, however, and the combination of the fundamental molecular vibrations are in the NIR spectral region. They are significantly weaker and enable direct measurement without sample preparation, while at the same time offering deep insights into the chemical and physical properties of the sample. The strongest overtone absorptions in the NIR range are displayed by compounds with OH, CH, NH, and SH bonds. Because the NIR spectrum represents the result of numerous overlapping absorption bands, it is normally evaluated with multivariate chemometric methods.
ANALYSES OF DIVERSE MATRICES
Near-infrared spectroscopy requires no sample preparation and can handle any sample matrix, no matter if it is powders or granulates, tablets or capsules, creams or gels, solutions or suspensions, polymer films or freeze-dried samples. Near-infrared spectroscopy can even perform determinations on contents sealed in transparent packaging such as glass and films. This is particularly appealing for incoming goods inspections and packaged end products. Handling is so easy that NIRS can be used directly in pharmacies and customs offices.
Near-infrared spectroscopy has long been considered one of the most important and versatile analytical techniques in the pharmaceutical industry– and not just because everybody in Pharma is talking about process analytical technologies (PAT) and Quality by Design (QbD). The decisive benefit of NIRS is the possibility of obtaining reliable analysis results in just seconds without any sample preparation or reagents whatsoever.
PAT AND QBD: IN SEARCH OF THE BEST METHOD
Drug manufacturing is undergoing a transformation. The FDA's stated goal is to cut development time for new drugs while at the same time significantly improving quality. This requirement can only be fulfilled with analytical techniques that monitor the entire process – from incoming raw materials to the final inspection. To achieve that, perfect PAT sensors are needed that enable "live" tracking of the manufacturing process. Near-infrared spectroscopy is the technique that makes this possible. An inline sensor monitors product quality in real time. This prevents out-of-specification products and reduces overall costs.
Calibration model for quantitative determination of water contentin powders. Karl Fischer titration is the reference method for the determination of the water content.
Reduction of water content in a pharmaceutical powder over time. Rapid and nondestructive NIR analysis makes it possible to determine the optimal moment for further processing in real time. The sensor is installed directly in the granulator.
GRANULATION AND DRYING
A key manufacturing process in the pharmaceutical industry is the granulation and drying process for powders that precedes tablet manufacturing. This process makes it possible to press powders into tablets in the first place. Near-infrared spectroscopy is the method of choice for determining the reaction endpoint when press ability is at the optimal point. Probes in the drier or granulator make it possible to track the process in real time. That reduces the process duration and thus increases the drying and granulation capacity of the system. At the same time, it minimizes the deviation from the required set-point values. Figure 2 shows a calibration model for water determination that correlates NIRS to Karl Fischer titration which is the reference method. The progressive diminution of the water content during the granulation process, measured by real-time NIRS, can be seen in Figure 3.
IN ACCORDANCE WITH INTERNATIONAL PHARMACOPOEIAS
As a secondary test method, NIRS is recommended in all of the key pharmacopoeias – from the European (Ph. Eur. 2.2.40) to the American (USP<1119>) to the Japanese pharmacopoeia.
Metrohm NIR Systems for example, offer users instruments that meet the standards for wavelength precision, reproducibility, and photometric noise. Numerous reference standards and user-friendly software make it easier for analysts to check the instrument requirements specified in the pharmacopoeias. The pharmaceutical version of Metrohm’s Vision software is fully validated and compliant with 21CFR Part 11. The company also offers complete IQ/OQ documentation and instrument performance certification(IPC). Documented parameters guarantee that the instrument performs properly. Further information: pharma.metrohm.com