Polymorph formation in fenofibrate in the absence and presence of polymer stabilizers: a low wavenumber Raman and differential scanning calorimetry study

In situ, variable temperature low wavenumber Raman spectroscopy and differential scanning calorimetry together with scanning electron microscope imaging were used to investigate polymorph formation in the non-hydrogen bonded, anti-cholesterol drug fenofibrate (FNB), in the absence and presence of two non-ionic polymeric stabilizers: triBlock copolymer pluronic-F127 (PF/127) and hydroxypropyl methyl cellulose (HPMC/E3). Low wavenumber Raman spectra show that metastable phase II formation occurs on initial cooling to 25 °C following the first heat-up to 100 °C for both pure FNB and FNB in the presence of PF/127, but not in the presence of HPMC/E3. Differential scanning calorimetry results on the other hand show that phase II of FNB crystallizes near 75 °C during the first heat-up of the drug in the presence of PF/127 but was not observed in the pure drug or the drug in the presence of HPMC/E3. These results are discussed in terms of molecular simulations carried out to determine the non-bonded interaction energies between the polymers and FNB.