Suspension for intravenous injection: image analysis of scanning electron micrographs of particles to determine size...

The purpose of this study is to determine the size and volume of large particles in a drug suspension by performing an image analysis of digital micrographs obtained by field emission, low voltage scanning electron microscopy (FE-LVSEM). The data obtained by this method are then used to select the appropriate imaginary component of the complete refractive index necessary for the software computation of particle size distribution measured using laser light diffraction. The application of FE-LVSEM involves four major elements: 1) the use of Anodisc inorganic aluminum oxide membrane filters for the image analysis of drug crystal particles > or = 350 nm having been isolated from suspension in order to determine the area, length, width, and other particle measurements; 2) the use of either a Thornley Everhart secondary electron detector or a MCP detector in the secondary electron mode directly above the specimen so as to produce a shadow-free digital image; 3) recording digital images as viewed normal to the crystal surface and at 45 degrees so as to image the edge of the crystal at a known angle; and 4) determination of drug particle volume from both views and the conversion of those volumes to an equivalent spherical volume.