More and more newly developed Active Pharmaceutical Ingredients (APIs) are crystalline and their bioavailability may therefore be low. In case the APIs cannot be solved in liquid solubilizers, the pharmaceutical industry faces the challenge to find the right polymeric solubilizers, additives, processing equipment and processing parameters (e.g. Hot-Melt Extrusion – HME) to be able to process them and obtain products with high bioavailability, long term stability and good drug release characteristics. Initially, such new crystalline APIs are often available in small quantities only. To investigate pure polymers, pure APIs and formulations of those (also with plasticizers and additives), simultaneous oscillatory rheometry and polarization light microscopy (with well-defined temperature profiles up to 300°C) can be used. Even with a very small amount of API, this rheo-optical method reveals, whether an amorphous solid solution (or amorphous or crystalline dispersions) is formed and whether a re-crystallization occurs either during the cooling run or with the storage time (stability). Simultaneous rheometry and polarization microscopy delivers efficiently significant and well-correlated rheological data and microscopic images. It provides on the one hand an efficient screening tool for HME formulation development and makes on the other hand rheological parameters for process development and optimization, as well as for modeling calculations for compounding and extrusion available. A hypothesis under discussion is that the long-term stability of HME pharmaceutical products my be improved as soon as a product is below its glass transition temperature at storage temperature. DMTA solid sample clamp measurements allow investigating the multifactorial impacts of e.g. APIs, additives, formulation and processing parameters on the glass transition behavior. Measuring data examples and microscopic images will be presented.