The focused ion beam technique: a useful tool for pharmaceutical characterization.

Focused ion beam (FIB) instrumentation, a hybrid of the scanning electron micrsocope, ion milling and computer-aided design systems, has special uses in the electronic and semiconductor industries as a tool for failure analysis and device development. This paper examines the pharmaceutical applications of the FIB, particularly microscopic analysis of microspheres. With the FIB, microsphere structures were peeled off, layer by layer, and the structure of each layer was simultaneously observed under scanning microscopy. The particles had a wrinkled but non-porous surface. Going deeper, some holes appeared, with size and numbers increasing toward the particle center. This unique method precisely investigated the inner structure of particles, layer by layer. Then, by FIB milling, samples were extracted with an accuracy of localization of 50nm from specific parts of the microspheres and prepared to a 200nm uniform thickness film for examination under transmission electron microscopy. The FIB method also has the potential for a wide range of other quantitative and qualitative analysis of dosage forms and materials.