Advanced structural characterisation of pharmaceuticals using nano-thermal analysis (nano-TA)

The production of drug delivery systems fabricated at the nano scale comes with the challenges of identifying reliable characterisation tools, especially for solid dosage forms. A full understanding of physicochemical properties of solid-state systems at a high spatial resolution is essential to monitor their manufacturability, processability, performance (dissolution) and stability. Nano-thermal analysis (nano-TA), a hybrid of atomic force microscopy (AFM) and thermal analysis, has emerged as a solution to address the need for complete characterisation of samples with surface heterogeneity. Nano-TA provides not only physical information using conventional AFM but also the thermal behaviour of these systems as an additional chemical dimension. In this review, the principles and techniques of nano-TA are discussed with emphasis on recent pharmaceutical applications. Building on nano-TA, the combination of this approach with infrared spectroscopic analysis is briefly introduced. The challenges and considerations for future development of nano-TA characterisation are also outlined.