The development of microthermal analysis and photothermal microspectroscopy as novel approaches to drug–excipient compatibility studies

Compositional Analysis of Low Quantities of Phase Separation in Hot-Melt-Extruded Solid Dispersions: A Combined Atomic Force Microscopy, Photothermal Fourier-Transform Infrared Microspectroscopy, and Localised Thermal Analysis Approach

“…Local Thermal Analysis (LTA) of Phase Separation Using Nano-Thermal Probes LTA has been used for the characterisation of multicomponent pharmaceutical systems at a micron scale (6,7,33). The introduction of the new nano-thermal probes allows for the characterisation probing a submicron level (7).…”

“…The introduction of the new nano-thermal probes allows for the characterisation probing a submicron level (7). Furthermore, the use of the nano-thermal probes in principle can increase the spatial resolution and reduce the thermal damage to the surrounding areas during each LTA test (7,33). LTA was used in this study to identify the particles observed in the PFM-AFM images.…”

“…In this study, the Wollaston thermal probe was coupled with the photothermal spectrometer to gain localised spectroscopic information of the formulations, such as chemical composition and physical forms of the components. This novel analytical technique has been increasingly used for chemical and physical identification of pharmaceutical-related materials (7)(8)(9)33). The wavelength of the energy absorption (the location of the PT peaks) of the photothermal measurements is the same as conventional IR measurements, but with slightly different relative peak intensities (9).…”

“…Early identification of phase separation using conventional macroscopic analytical methods, such as DSC, has been shown to be difficult due to the low quantity of separated material, and, when using imaging methods such as SEM, there are difficulties associated with identifying the physical and chemical nature of the observed structures (6). This study proposes a new way of addressing this problem by combining pulsed force mode atomic force microscopy (PFM-AFM) with the newly developed technique of localised nano-thermal analysis (LTA) and photothermal Fourier-Transfer Infrared (PT-FTIR) microspectroscopy (7)(8)(9). A previous study demonstrated the potential of micro-thermal analysis in the characterisation of hot-melt-extruded formulations (10).…”

Thermogravimetric detection of incompatibilities between atenolol and excipients using multivariate techniques

“…These are isothermal microcalorimetry [8,9], high-sensitivity DSC (HSDSC) [10] and micro-thermal analysis [11,12]. These advanced analytical methodologies are useful for the investigation of compatibility, but they have also some limitations, among others, they are expensive and are not widespread in pharmaceutical laboratories.…”