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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Crystal Growth & Design; v. 17, n. 5, p. 2622-2630, MAY 2017.
• Citações Web of Science: 11

Resumo

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)

• Processo FAPESP: 12/05616-7 - Caracterização no estado sólido de fármacos de ação anti-convulsionantes e antidepressivos: Planejamento de novas formas cristalinas.
• Beneficiário: Paulo de Sousa Carvalho Júnior
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/25694-0 - Obtenção, caracterização e avaliação de novas formas sólidas cristalinas de fármacos usados no tratamento da tuberculose
• Beneficiário: Luan Farinelli Diniz
• Modalidade de apoio: Bolsas no Brasil - Mestrado