Theoretical and experimental study of fenofibrate and simvastatin

• Published in: Journal of molecular structure Vol. 1149; pp. 683 - 693
• Main Authors: Nicolás Vázquez, Inés, Rodríguez-Núñez, Jesús Rubén, Peña-Caballero, Vicente, Ruvalcaba, Rene Miranda, Aceves-Hernandez, Juan Manuel
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05-12-2017
• Subjects: DFT-B3LYP; DFT-PBE1PBE; Fenofibrate-simvastatin mixtures; IR analysis; Theoretical chemistry; Thermal analysis; X-ray diffraction; Fenofibrate-simvastatin mixtures; X-ray diffraction; DFT-B3LYP; IR analysis; DFT-PBE1PBE; Thermal analysis; Theoretical chemistry
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2017.08.044

Fenofibrate, an oral fibrate lipid lowering agent, and simvastatin, which reduces plasma levels of low-density lipoprotein cholesterol, are active pharmaceutical ingredients (APIs), currently in the market. We characterized these APIs by thermal analysis and conducted X-ray powder diffraction techniques. Studies should be carried out in the formulation stage before the final composition of a polypill may be established. Thus, it was found in thermochemical studies that both compounds present no chemical interactions in an equimolar mixture of solid samples at room temperature. Theoretical studies were employed to determine possible interactions between fenofibrate and simvastatin. A very weak intramolecular hydrogen bond is formed between the hydroxyl group (O5H5) of the simvastatin with chlorine and carbonyl group (C11O4, C1O2) of the fenofibrate molecule. These weak energy hydrogen bonds have no effect on the chemical stability of the compounds studied. The results were obtained using Density Functional Theory methods; particularly the BPE1BPE and B3LYP functional and 6-31++G** basis set. The values of energy show good approximation when are compared with similar calculations previously reported. Infrared spectra of monomers and dimers were obtained via theoretical calculations.
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•Methods of DFT were used for obtaining the optimized geometry of fenofibrate and simvastatin.•Interatomic distances obtained by theoretical methods are in good agreement with the X-ray diffraction data.•Theoretical calculations of the compounds studied show few weak hydrogen bonds.•The obtained experimental results show not chemical interactions of fenofibrate and simvastatin in solid state.•There is a good agreement between theoretical and experimental IR spectra.