Modulating the water solubility and thermal stability of the anti-tuberculosis drug Isoniazid via multicomponent crystal formation

Author(s)

Diniz, Luan F. ^[1] ; Souza, Matheus S. ^[1] ; Carvalho, Jr., Paulo S. ^[1] ; Correa, Charlane C. ^[2] ; Ellena, Javier ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Fis Sao Carlos, CP 369, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Fed Juiz de Fora, Inst Ciencias Exatas, Dept Quim, BR-36036330 Juiz De Fora, MG - Brazil

• Document type: Journal article
• Source: Journal of Molecular Structure; v. 1171, p. 223-232, NOV 5 2018.
• Web of Science Citations: 0

Abstract

In this paper three novel salts of the anti-tuberculosis drug Isoniazid (INH) with the GRAS salt formers (oxalic, maleic and methanesulfonic acids) were supramolecularly synthesized by solvent evaporation method. Aiming to expand the diversity of supramolecular synthons of this drug as well as obtaining new solid forms with enhanced solubility and thermal stability, these salts namely oxalate (INH-OXA), maleate (INH MAL) and mesylate (INH-MES) were fully characterized by X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR) and thermal (TGA, DSC, HSM) techniques. At the same time, salts' solubility was explored. Analysis of the crystal structures and packings were analyzed in details, showing that the INH salts exhibit layered structures stabilized by N-H center dot center dot center dot O, C-H center dot center dot center dot O and It pi...pi 17 interactions. The salt formations were confirmed from the FT-IR and FT-Raman spectra and their thermal behaviors indicate that INH-OXA and INH-MES are thermally more stable than the corresponding INH. The equilibrium solubilities of these salts, in different buffered media, were evaluated and both INH-MAL and INH-MES were found to be more soluble (similar to 3 fold) than INH. Therefore, the present study proved that salt formation is an efficient strategy to enhance solubility and thermal stability of INH. (C) 2018 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 15/25694-0 - Obtaining, characterization and evaluation of novel crystalline solid forms of drugs used treatment of tuberculosis
• Grantee: Luan Farinelli Diniz
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/05616-7 - Solid-state characterization of anticonvulsant and antidepressant phamaceutical compounds: Design of new crystal forms.
• Grantee: Paulo de Sousa Carvalho Júnior
• Support Opportunities: Scholarships in Brazil - Doctorate