Structure elucidation of silica-based core–shell microencapsulated drugs for topical applications by cryogenic scanning electron microscopy

We present here a technology to microencapsulate drugs by the sol–gel process, and cryo-SEM methodology that allows the nanostructural characterization of the formed capsules in their native state without any artifacts, related to their drying prior to imaging. The methodology utilizes three signals generated by the electron beam scanning the specimen: Secondary electrons, backscattered electrons, and x-rays. The first gives topographical information of the fracture-surface of the thermally-fixed specimen, the second gives contrast between elements of different atomic numbers, and the third allows the identification of those elements. Combined, the three signals provide full microstructural characterization of the studied specimen. Using this methodology, we were able to demonstrate that the sol–gel technology does indeed enable the encapsulation of two hydrophobic active molecules with a silica shell. This technology allows the active ingredient in the drug product to slowly migrate from the microcapsule onto the skin, thus obtaining the desired effect with minimal side-effects, as was exhibited in several clinical studies. The successful application of the cryo-SEM methodology in this case, demonstrates that it can be used to characterize a wide range of liquid-phase suspensions, in their native state, with minimal specimen preparation or imaging artifacts.