The development of thermally assisted particle manipulation and thermal nanointeraction studies as a means of investigating drug-polymer interactions

This investigation outlines the development of two novel techniques, thermally assisted particle manipulation and thermal nanointeraction studies, to examine the interaction between materials during heating. Dispersions of paracetamol in polyethylene glycol 6000 were prepared and studied using microthermal analysis in a range of modes. The localised thermomechanical analysis (L-TMA) responses showed intermediate responses compared to the pure materials. Thermally assisted particle manipulation was used to place a single particle of PEG on the paracetamol surface and the assembly analyzed using L-TMA as a function of position, with the intermediate response seen at the interface between the two materials. Thermal nanointeraction studies, whereby nanosampled PEG was heated in the immediate proximity of the paracetamol, indicated that the process was kinetically controlled and could be interpreted in terms of the molten PEG influencing the apparent melting of the paracetamol. Near-field photothermal IR was used to identify the nature of the material on the probe tip; we provide the first quantitative evaluation of the amount sampled when carrying out thermally assisted nanosampling (circa 500 fg). The investigation has therefore demonstrated that these methods maybe used as a novel approach to studying thermal interactions between pharmaceutical materials. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1551-1563, 2008.