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

Author(s)

Holanda, Bruno B. C. ^[1] ; Alarcon, Rafael T. ^[1] ; Gaglieri, Caroline ^[1] ; de Souza, Aguinaldo R. ^[1] ; Castro, Ricardo A. E. ^[2] ; Rosa, Paulo C. P. ^[3] ; Tangerino, Debora J. A. ^[3] ; Bannach, Gilbert ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Sci, BR-17033260 Bauru, SP - Brazil

^[2] Coimbra Univ, Coll Pharm, P-3000578 Coimbra - Portugal

^[3] Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY; v. 136, n. 5, p. 2049-2062, JUN 2019.
• Web of Science Citations: 0

Abstract

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:INCT5:1, 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 1mol:1mol. 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 0.1M 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. (AU)

• FAPESP's process: 13/09022-7 - Thermoanalytical studies, synthesis and characterization of the solid co-crystals of antibiotics (fluoroquinolones) with some co-formers
• Grantee: Massao Ionashiro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/03460-6 - Structural modification of triglycerides aiming new monomers and polymers, using different synthetic routes: microwave irradiation and photopolymerization
• Grantee: Rafael Turra Alarcon
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07296-2 - CDMF - Center for the Development of Functional Materials
• Grantee: Elson Longo da Silva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/22338-9 - Study of the interaction between drugs and human serum albumin (HSA) based on computer simulation, DFT and TDDFT, experiments of electronic circular dichroism, ECD, and determination of the bond formation constant
• Grantee: Aguinaldo Robinson de Souza
• Support Opportunities: Regular Research Grants