Chemical Imaging by Dissolution Analysis: Localized Kinetics of Dissolution Behavior to Provide Two-Dimensional Chemical Mapping and Tomographic Imaging on a Nanoscale.

A new approach to achieving chemical mapping on a nanoscale is described that can provide 2D and tomographic images of surface and near-surface structure. The method comprises dissolving material from the surface of the sample by applying a series of aliquots of solvent, then analyzing their contents after removing them; in between exposures, the surface is imaged with atomic force microscopy. This technique relies on being able to compensate for any drift between images by use of software. It was applied to a blend of two polymers, PMMA and PS. The analytical data identified the material that was dissolved, and the topography images enabled the location of the various materials to be determined by analyzing local dissolution kinetics. The prospects for generalizing the approach are discussed.

Thermal probe based analytical microscopy: thermal analysis and photothermal Fourier-transform infrared microspectroscopy together with thermally assisted nanosampling coupled with capillary electrophoresis.

In this study, we have demonstrated that a scanning probe microscope (SPM) can be used for thermally assisted nanosampling (TAN) with subsequent analysis by capillary electrophoresis (CE). Localized thermomechanical analysis (L-TMA) and photothermal Fourier-transform infrared (PT-FTIR) microspectroscopy can also be employed using the same probe, thus illustrating how a single instrument can carry out a number of different complementary analytical measurements. Benzoic acid and 4-hydroxybenzoic acid were manipulated with a heated Wollaston wire probe and successfully deposited onto the surface of a piece of CE capillary tubing. The deposited samples were then separated with CE. L-TMA and PT-FTIR were also used to characterize these materials. We have also demonstrated how a nanosample of a nonparticulate material can be taken and then deposited onto the surface of an inert matrix. TAN of a nonparticulate material was explored using polyethylene as the analyte and fluorene as the matrix. These examples show that thermal probe techniques provide a versatile "tool box" of modes of analysis with the potential to analyze a wide range of samples in a spatially resolved way.

A study of phase separation in peptide-loaded HPMC films using T(zero)-modulated temperature DSC, atomic force microscopy, and scanning electron microscopy.

Despite the widespread use of drug-loaded polymeric systems, there is still considerable uncertainty with regard to the nature of the distribution of the drug within the polymer matrix. The aim of this investigation was to develop thermal and microscopic techniques whereby the miscibility and spatial distribution of a model peptide, cyclosporin A (CyA), in hydroxypropyl methylcellulose (HPMC) films may be studied. The new technique of T(zero)-modulated temperature differential scanning calorimetry (T(zero) MTDSC), scanning electron microscopy (SEM), and pulse force mode atomic force microscopy (PFM-AFM) were used in conjunction to study films prepared using a solvent evaporation process, with a solvent extraction study performed to elucidate the nature of the observed phases. T(zero) MTDSC studies showed glass transitions for both the HPMC and CycA, with the T(g) for the HPMC and CycA seen for the mixed systems. SEM showed two spherical phases of differing electron density. PFM-AFM also showed spheres of differing adhesion that increased in size on addition of drug. Pixel intensity analysis indicated that the smaller spheres corresponded to CycA. Exposure of the films to dichloromethane, in which CycA is soluble but HPMC is not, resulted in the presence of voids that corresponded well to the spheres suggested to correspond to the drug. It was concluded that the system had undergone extensive or complete phase separation, and that the thermal and microscopic techniques outlined above are an effective means by which this issue may be studied.