Potential of attenuated total reflection infrared and near-infrared spectroscopic imaging for quality assurance/quality control of solid pharmaceutical dosage forms

Methods that can spatially characterise the distribution of components throughout solid pharmaceutical dosage forms are of great interest to ensure product quality and enhance production speed. Infrared (IR) spectroscopy in combination with traditional microscopy has been available for more than a quarter of a century. Until recently, a very time-consuming step-by-step "mapping" procedure was necessary to determine large sample areas. This drawback considerably limited the use of this technique for many applications. With the development of novel imaging systems based on Focal Plane Array (FPA) detector technology, which enable large areas to be measured simultaneously with a high local resolution, it is now possible to rapidly collect high contrast images of large sample areas. The state of the art in Attenuated Total Reflection (ATR)-IR and Near-Infrared (NIR) imaging techniques is reviewed and discussed indicating that only few pharmaceutical applications have been reported in the literature. This work suggests that both ATR-IR and NIR imaging have considerable value for the chemical and functional characterisation of complex solid pharmaceutical dosage forms. Two novel applications are presented in detail: 1. Chemical visualisation of variations in film coat uniformity on tablets. 2. Chemical mapping of the distribution and relative abundance of a model protein in polymer matrix tablets, immediately after processing and during the release phase. It is demonstrated that both techniques provide rapid information about the type, distribution and relative abundance of drugs and/or excipients within a solid pharmaceutical dosage form, thus having great potential for a variety of pharmaceutical Quality Assurance/Quality Control applications.