Polymorphism of gemfibrozil: Investigation by thermal and spectroscopic methods

• Published in: Thermochimica acta 2019-05, Vol.675, p.113-118
• Main Authors: Holanda, Bruno B.C., Bannach, Gilbert, Ramos Silva, M., Eusébio, M. Ermelinda S., Castro, Ricardo A.E.
• Format: Article
• Language: English
• Subjects: Gemfibrozil; Memory effect; Polymorphism; Thermal analysis
• ISSN: 0040-6031; 1872-762X
• DOI: 10.1016/j.tca.2019.03.026

The polymorphism of gemfibrozil was studied by thermal and spectroscopic analysis. GEM has two crystalline polymorphic forms with monotropic relationship. It was observed a crysttaline memory effect on GEM. GEM has an amorphous state that can be confirmed at temperature −34 °C. The crystalline polymorphic forms probably must have a similar structure. The knowledge of polymorphism of active pharmaceutical ingredient is relevant in the pharmaceutical field. In this work, a multidisciplinary approach involving differential scanning calorimetry, polarized light thermal microscopy, X-ray powder diffraction and attenuated total reflectance infrared spectroscopy was used to investigate polymorphism of gemfibrozil (GEM), an important fibric acid derivative, in melting cooling/heating cycles. An amorphous phase, Tg = −34 °C, and two monotropic crystalline polymorphs with very close melting temperatures, form I, Tfus,I = 59.0 °C, and form II, Tfus,II = 58.0 °C, were identified, being form I the stable phase. In some experiments the forms were obtained concomitantly. The crystallization process seems to be dependent on molten liquid memory. Thereby, this effect could be due to low molecular mobility in the liquid state resulting from the relatively long carbon chain structure of GEM.