. Concluding remarks
In the case of pharmaceutical solids, recent work using atomic force microscopy (AFM), terahertz spectroscopy and transmission electron microscopy (TEM) suggests that these techniques will be important for characterising mechanically treated samples and understanding changes which occur during such processing. For example, there are particle–particle effects – especially important during compression in a tablet containing various components. In the case of aspirin (acetylsalicylic acid) and dicalcium phosphate, when the excipient was attached to the tip of the AFM cantilever and different pressures and contact times under various humidity conditions there was evidence for enhanced reactivity induced by surface contact with excipient.91 Terahertz spectroscopy has emerged as a sensitive method of monitoring changes in the solid form during mechanical activation,56,156 whereas TEM has been shown to be a powerful technique for characterising the size and shape of particulates generated mechanochemically, as well as determining their crystal form (see Fig. 20). TEM can also be used to identify defects in pharmaceutical crystals (see Fig. 21), and will enable a greater understanding of how defects introduced into crystals during mechanical processing influence material properties – for example a link between defects in theophylline crystals and crystal fracture has been established.160