Generation and characterization of standardized forms of trehalose dihydrate and their associated solid-state behavior

Trehalose dihydrate is a nonreducing disaccharide which has generated great interest in the food and pharmaceutical industries. However, it is well recognized that considerable batch to batch variation exists for supposedly identical samples, particularly in terms of the thermal response. In this investigation, two standardized forms of trehalose dihydrate were generated using two distinct crystallization pathways. The two batches were characterized using scanning electron microscopy, X-ray powder diffraction, and FTIR. The thermal responses of the two forms were then studied using modulated temperature differential scanning calorimetry (MTDSC) and thermogravimetric analysis (TGA). In particular, we describe the technique of quasi-isothermal MTDSC as a means of studying the change in equilibrium heat capacity as a function of temperature. Finally, variable temperature FTIR was utilized to assess the change in bonding configuration as a function of temperature. SEM revealed significant differences in the continuity and grain structure of the two batches. The TGA, MTDSC, and quasi-isothermal MTDSC studies all indicated significant differences in the thermal response and water loss profile. This was confirmed using variable temperature FTIR which indicated differences in bond reconfiguration as a function of temperature. We ascribe these differences to variations in the route by which water may leave the structure, possibly associated with grain size. The study has therefore demonstrated that chemically identical dihydrate forms may show significant differences in thermal response. We believe that this may assist in interpreting and hence controlling interbatch variation for this material

Development of photothermal FTIR microspectroscopy as a novel means of spatially identifying amorphous and crystalline salbutamol sulfate on composite surfaces

Photothermal Fourier transform infrared (FTIR) microspectroscopy (PTMS), involving the combination of FTIR spectroscopy with atomic force microscopy, has been used to examine compacts of amorphous and crystalline salbutamol sulfate in order to assess the ability of the technique to distinguish between different physical forms in a multicomponent material. Samples of amorphous and crystalline material were assessed using modulated temperature differential scanning calorimetry (DSC), atomic force microscopy, microthermal analysis, and conventional FTIR. Mixed compacts were then prepared such that verification of the location of the forms present was possible via topography and localized thermal analysis. PTMS studies were then performed on selected interrogation points, with spectra obtained which were largely intermediate between those corresponding to the two individual forms. Calculation of the thermal diffusivity indicated a resolution for the technique corresponding to a hemisphere of a major diameter in the region of 40 μm, which is large in relation to the particle sizes involved. However, distinction into amorphous, crystalline, and indeterminate categories was possible using chemometric analysis (hierarchical cluster analysis and principal component analysis). Good agreement was found between the identification methods for the mixed systems. The study has therefore shown the potential, as well as identifying the limitations, of using PTMS as a means of spatially identifying components in complex materials