ABSTRACT
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.
Subject(s)
Pharmaceutical Preparations , Drug Stability , Injections, Intravenous , Itraconazole/administration & dosage , Itraconazole/chemistry , Itraconazole/standards , Microscopy, Electron, Scanning , Particle Size , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/standards , Powders , Solubility , Surface Properties , SuspensionsABSTRACT
Four dogs with disseminated aspergillosis caused by Aspergillus terreus were treated with oral itraconazole for 190 to 1095 days. Infection was eliminated in 1 dog. Two dogs were treated for 1000 and 1095 days but were eventually euthanased 572 and 485 days after treatment was stopped. At necropsy both dogs had widespread aspergillosis. The fourth dog was euthanased for other reasons after 190 days of treatment when it was showing a good clinical response although there was radiographic evidence that the disease was progressing.