4.5.3. Transmission Electron Microscopy (TEM)

Conventional transmission electron microscopes are electron-optical instruments analogous to light microscopes [130]. The main difference being that in TEM, the illumination of the specimen is by an electron beam as opposed to light. An increase in acceleration voltage of the electrons directly results in an increase in resolution. However, a reduction in contrast results from increasing acceleration voltage as a consequence of the scattering of the electrons being decreased at higher velocity [131].

TEM is particularly useful for the study of colloidal and nanostructured drug delivery systems including NCM [88,132]. Much like SEM, TEM is more useful in determining surface morphology, differences in crystal habit, and determining particle shape. TEM is widely the most applied method for evaluation, is used in many characterisation approaches, and is considered the gold standard for PS determination.
