Infrared spectroscopy is a common analytical method in the pharmaceutical industry. However, the analysis of powder products can be a challenge. This is particularly true for inorganic materials. The present article introduces the recently developed solvent infrared spectroscopy (SIRS) technique. It is based on attenuated total reflection (ATR) infrared spectroscopy and allows the analysis of powders with minimal sample preparation.
Background
Many products in the pharmaceutical industry and in other sectors are powders. Such powders can be the active ingredient itself, but also an excipient such as a binder or a preservative. For quality assurance, the products need to be analyzed in a reliable and accurate manner. Generally speaking, there are quite a few analytical techniques available for this purpose. However, many of them require sophisticated sample preparation and handling, involve expensive equipment, and need extensive measurement times. The list of prominent examples includes wet analytical chemistry, chromatography, X-ray diffraction, and electron microscopy. For an overview, see 1 .
In recent years, vibrational spectroscopy in terms of mid- and nearinfrared (IR) absorption and Raman scattering spectroscopy have become very popular. Especially, the attenuated total reflection (ATR) approach in IR spectroscopy offers many advantages such as minimal sample preparation, excellent reproducibility, and experimental simplicity. In an ATR-IR experiment, the sample is put on top of the socalled internal reflection element (IRE), i.e. a crystalline material with high refractive index in which the IR radiation is propagating. At the surface of the IRE the radiation undergoes total internal reflection. The sample interacts with the exponentially decaying evanescent field. Therefore, even opaque samples can be analyzed. The reflected beam eventually carries the information about the absorption spectrum of the sample.
The applicability of the conventional ATR technique, however, is limited when powders with a high refractive index close to that of the IRE are the measurement object. Such samples lead to experimental artifacts, which make the interpretation of the spectra difficult. A particularly challenging class of materials are inorganic and ceramic compounds as they do usually not only have a high refractive index but also a limited number and strength of absorption features. Therefore, they are rarely analyzed by ATR-IR spectroscopy. Instead, transmission IR measurements are performed, e.g. after preparing pellets with potassium bromide. This however is a means of sample preparation and is not desirable.
The SIRS Method
To overcome the aforementioned shortcoming of the conventional ATR-IR method, the solvent infrared spectroscopy (SIRS) approach has been proposed recently.2 In brief, a powder or porous solid is placed on the ATR crystal and fixed mechanically, usually with a metal clamp. In the second step, a droplet of a solvent is added to fill the void spaces and wet the crystal. Then, the IR spectrum is recorded and compared to that of the pure solvent. This experimentally simple approach is illustrated in Figure 1a and 1b.
Figure 1. Schematic illustration of the experimental SIRS approach. Panel (a) depicts the classical ATR-IR method and panel (b) shows the situation with the solvent added.In order to highlight the effect of adding a solvent, Figure 2 depicts the spectra of a titania nanopowder with and without the solvent ethanol. In addition, the pure solvent spectrum and its difference spectrum with the SIRS spectrum are plotted. The spectra were recorded on a Bruker Vertex 70 equipped with a diamond ATR unit. The ATR-IR spectrum of titania shows virtually no specific or distinguishable features aside from the broad absorption band at the lowwavenumber end of the spectrum. This makes a meaningful analysis and interpretation difficult. When the solvent is added, the resulting SIRS spectrum is dominated by the signatures of the pure solvent as can be seen from the comparison with the ethanol spectrum (a detailed analysis of alcohol spectra can be found in a recent article3 ). The two spectra, however, look very similar only at first glance. As the solvent interacts with the surface of the particles at the molecular level, the solvent’s vibrational structure is modified. For example, the formation of hydrogen bonds leads to charge transfer and alterations in the strengths of the covalent bonds. Consequently, they vibrate with a slightly different frequency in the presence of the particles. The difference spectrum of the pure solvent and the SIRS spectra emphasizes this. For instance, peak shifts manifest as S-shaped features in the difference spectrum. When peaks are not shifted but altered in amplitude, the difference spectrum reveals a positive or negative peak as can be seen for multiple peaks in the difference spectrum of Figure 2d. Moreover, the broad OH stretching band of ethanol is significantly altered in its overall shape. This is highlighted in the inset diagram where the OH bands with and without solvent are absorbance-normalized and subtracted. The detailed analysis of the spectral changes allows deducing information about the surface chemistry of the particles. Further insights can be gained by using different solvents in combination with the same powder.2 Doing this systematically allows a full picture to be obtained.
Figure 2. Schematic illustration of the experimental SIRS approach. Panel (a) depicts the classical ATR-IR method and panel (b) shows the situation with the solvent added.
Advantages and Disadvantages
Like any method, the described SIRS approach has advantages and disadvantages. A big benefit is its experimental simplicity and the fact that the samples do not need to be pre-treated. Furthermore, standard solvents such as alcohols and water may be sufficient to obtain all the information needed. However, systematic tests are necessary in the beginning in order to identify suitable candidates for a given powder. A disadvantage is that the information provided is of indirect nature. This means that the impact of the powder on the solvent is monitored rather than the powder itself. Consequently, the meaningful interpretation of the data requires experience. This is particularly true for the analysis of unknown powder materials. On the other hand, for routine applications like the classification of a powder, unsupervised methods such as the use of principal component analysis (PCA) for analyzing the SIRS data may be sufficient. In this respect, the SIRS method has a great potential for becoming a means of routine powder analysis.
Acknowledgment
The author thanks Heinz-Dieter Kurland, Janet Grabow, and Frank Müller (University of Jena, Germany) for providing the titania nanopowder. Furthermore, support from the Deutsche Forschungsgemeinschaft (DFG) through grant KI1396/6-1 (DFG priority program SPP1980) is gratefully acknowledged.
References
- S.R. Byrn, G. Zografi, X. Chen, Particle and Powder Analysis, in Solid State Properties of Pharmaceutical Materials, John Wiley & Sons, Hoboken, 2017.
- J. Kiefer, J. Grabow, H.-D. Kurland, F.A. Müller, Characterization of Nanoparticles by Solvent Infrared Spectroscopy, Analytical Chemistry 87 (2015) 12313-12317.
- J. Kiefer, S. Wagenfeld, D. Kerle, Chain length effects on the vibrational structure and molecular interactions in the liquid normal alkyl alcohols, Spectrochimica Acta A 189 (2018) 57-65.
Author Biography
Prof. Dr. Johannes Kiefer is Chair Professor and Head of the Division Technische Thermodynamik at the University of Bremen, Germany. In addition, he is an Honorary Professor at the University of Aberdeen, Scotland, and he holds a guest professorship of the Erlangen Graduate School in Advanced Optical Technologies (SAOT) at the University Erlangen-Nuremberg, Germany. His research interests are the areas of developing and applying spectroscopic techniques for the characterization of advanced materials and processes.