National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca
Crystal and molecular structure determination on powders:
innovative practical solutions with applications in
developing new biologically active compounds
Characterization of pharmaceutical compounds and the analysis of complex modern formulations, together with an increasing need for data to support regulatory submissions, means that the pharmaceutical industry now depends on a range of analysis technologies.
In recent years with the advent of “high-throughput” crystallization techniques, there is an increased demand for fast and reliable structural characterization methods. Both powder X-ray diffraction (PXRD) and solid-state nuclear magnetic resonance (SS-NMR) spectroscopy meet these requirements, as they do not depend on the synthesis of high quality single crystals. They are already recognized as valuable techniques in many areas of drug discovery, development and manufacture.
Powder X-Ray Diffraction is used to: determine crystal structures, screen for polymorphs or hydrates, detect changes in morphology or crystalline state of active ingredients (e.g. during processing or at non-ambient conditions), detect and quantify crystalline impurities (in some cases down to 0.05%), determine the crystallinity or the crystallite size of a compound, analyze and optimize final dosage forms.
Solid-State NMR Spectroscopy is used for: identification of polymorphs and detection of polymorphic purity, solid state identification of API, deformulation of solid state pharmaceutical forms, characterization of amorphous compounds and quantification, new formulations developments allowed by SS-NMR characterization, interaction of API with excipients.
The present project aims at investigating various possible ways to combine powder X-ray diffraction (PXRD), solid-state nuclear magnetic resonance (SS-NMR), and molecular modeling with the purpose of speeding up the process of crystal structure refinement. In particular, it will be studied the extent that intermolecular distances constraints obtained by suitable SS-NMR techniques can remove ambiguities that may occur in deriving an initial structural model and / or in assigning the correct spatial group from the measured powder X-ray diffraction pattern.
