Reducing the Hygroscopicity of the Anti-Tuberculosis Drug (S,S)-Ethambutol Using Multicomponent Crystal Forms

Author(s)

Diniz, Luan F. ; Carvalho, Jr., Paulo S. ; de Melo, Cristiane C. ; Ellena, Javier

• Document type: Journal article
• Source: Crystal Growth & Design; v. 17, n. 5, p. 2622-2630, MAY 2017.
• Web of Science Citations: 11

Abstract

Ethambutol (ETB) is a chiral dibasic compound formulated and marketed as the (S,S)-ethambutol dihydrochloride, (S,S)-EDH, to treat tuberculosis. It is administered orally in a solid formulation composed of isoniazid, rifampicin, and pyrazinamide as a fixed-dose combination tablet. Because of its high hygroscopicity, (S,S)-EDH is known for catalyzing the degradation of isoniazid by rifampicin to yield isonicotinyl hydrazone. In order to avoid or even minimize these mutual drug drug interactions, in this work we have focused on the development of less hygroscopic multicomponent solid forms of ETB. Four salts of this drug, namely, oxalate (ETBOXA), maleate, terephthalate, and trichloroacetate, were prepared via supramolecular synthesis by the slow evaporation method and characterized by X-ray diffraction (single crystal X-ray diffraction, powder X-ray diffraction), spectroscopic (Fourier transform-infrared), and thermal (thermogravimetric analysis, differential scanning calorimetry, hot stage microscopy) techniques. The hygroscopic nature of these salts, including (S,S)-EDH, were evaluated, and all of them were found to be hygroscopic, with the exception of ETBOXA. (AU)

• 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
• 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