Abstract
Organic and biological compounds (especially those related to the pharmaceutical industry) have always been of great interest for researchers due to their importance for the development of new drugs to diagnose, cure, treat or prevent disease. As many new API (active pharmaceutical ingredients) and their polymorphs are in nanocrystalline or in amorphous form blended with amorphous polymeric matrix (known as amorphous solid dispersion—ASD), their structural identification and characterization at nm scale with conventional X-Ray/Raman/IR techniques becomes difficult. During any API synthesis/production or in the formulated drug product, impurities must be identified and characterized. Electron energy loss spectroscopy (EELS) at high energy resolution by transmission electron microscope (TEM) is expected to be a promising technique to screen and identify the different (organic) compounds used in a typical pharmaceutical or biological system and to detect any impurities present, if any, during the synthesis or formulation process. In this work, we propose the use of monochromated TEM-EELS, to analyze selected peptides and organic compounds and their polymorphs. In order to validate EELS for fingerprinting (in low loss/optical region) and by further correlation with advanced DFT, simulations were utilized.
Highlights
Many pharmaceutical compounds may exist as polymorphs
In order to establish a fairly conclusive screening and identification methodology to readily differentiate among various organic molecular crystals and their polymorphs, we first analyzed by energy loss spectroscopy (EELS) various “reference” organic crystals; in most of the cases several characteristic low loss < 20 eV
From our obtained results it seemed that the use of transmission electron microscope (TEM)–EELS (Figure 2) with a monochromatic source (0.2 eV resolution) was necessary to reveal fine spectral details in the low loss EELS region for organic compounds, otherwise without its use many spectral fine details would not have been clearly distinguishable
Summary
Many pharmaceutical compounds may exist as polymorphs (e.g., they crystallize into different packing arrangements having the same chemical formula). Drug polymorphism is critically important in the pharmaceutical industry, as many of the solid-state properties of a compound are dependent on its polymorphic form. When a drug or active pharmaceutical ingredient (API) is approved to be released into the market to be used for medication purposes, it is important that the marketed polymorphic form is well characterized (e.g., rules under US Food and Drug Administration—FDA in United States and European Medicines Agency—EMA in European countries). It is very important to characterize all the forms, not just only the marketed ones, as it might be possible that some polymorphic forms could have (or not) the same therapeutic effects as the marketed API, or it can be harmful for health and the environment [3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
