In situ characterization of polymorphic forms the potential of Raman techniques

The use of hot-stage Raman microscopy - the direct coupling of Raman spectroscopy and thermomicroscopy - is demonstrated for the drug substances paracetamol and lufenuron. Paracetamol is a well-known analgesic and antipyretic drug, for which three polymorphic forms are currently known. Lufenuron is a benzoylphenyl urea derivative that has been classified as a chitin synthesis inhibitor. It is indicated for the use in pets for the prevention and control of flea population and used in crop protection for the control of Lepidoptera, Western Flower thrips and rust mites. It is the first time that the polymorphism of lufenuron is addressed. All known modifications of paracetamol and lufenuron were produced and identified by hot-stage Raman microscopy. A close correlation of thermal and spectroscopic information was achieved by this combination of techniques. For lufenuron a series of new polymorphic forms were found and characterized. Raman spectroscopy allowed to identify the thermodynamic stable form A as the one which is marketed in tablets.