Thermal studies, degradation kinetic, equilibrium solubility, DFT, MIR, and XRPD analyses of a new cocrystal of gemfibrozil and isonicotinamide

A synthesis of a novel pharmaceutical cocrystal of the gemfibrozil (GEM) with the isonicotinamide (INCT) as coformer was carried out using the mechanochemical method of solvent drop grinding. The cocrystal formation was evidenced using the X-Ray powder diffraction, medium infrared spectroscopy, comp...

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Bibliographic Details
Published in:Journal of thermal analysis and calorimetry 2019-06, Vol.136 (5), p.2049-2062
Main Authors: Holanda, Bruno B. C., Alarcon, Rafael T., Gaglieri, Caroline, de Souza, Aguinaldo R., Castro, Ricardo A. E., Rosa, Paulo C. P., Tangerino, Débora J. A., Bannach, Gilbert
Format: Article
Language:English
Subjects:
Analytical Chemistry
Bioavailability
Buffers
Calorimetry
Chemistry
Chemistry and Materials Science
Degradation
Differential scanning calorimetry
Differential thermal analysis
Diffraction
Fibric acids
Formulations
Gemfibrozil
Infrared analysis
Infrared spectroscopy
Inorganic Chemistry
Measurement Science and Instrumentation
Phosphates
Physical Chemistry
Polymer Sciences
Potassium phosphates
Sodium acetate
Solubility
Storage temperature
X ray powder diffraction
X-rays
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Summary:A synthesis of a novel pharmaceutical cocrystal of the gemfibrozil (GEM) with the isonicotinamide (INCT) as coformer was carried out using the mechanochemical method of solvent drop grinding. The cocrystal formation was evidenced using the X-Ray powder diffraction, medium infrared spectroscopy, computational methods (DFT), simultaneous thermogravimetric-differential thermal analysis (TG/DTG–DTA), and differential scanning calorimetry. The association of techniques used to analyze all proportion synthetized (GEM:INCT—5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5) showed formation of the cocrystal in the proportion of 1 mol:1 mol. Furthermore, kinetic studies were performed to determine the stability of the cocrystal formed, possible shelf time (5% degradation), and best storage temperature. The dissolution profiles of GEM and GEM:INCT were collected using 0.1 M HCl, pH 4.5 sodium acetate buffer, water, and potassium phosphate buffer at pH 5.8, pH 6.8, and pH 7.4. The results demonstrate that the cocrystal exhibits superior apparent maximum solubility relative to the pure drug with a high solubility in alkaline environment. Finally, the study shows that the cocrystal of gemfibrozil with isonicotinamide can be applied in new solid oral dosage formulations of enhanced bioavailability.
ISSN:1388-6150
1588-2926
DOI:10.1007/s10973-018-7873-8